Neoadjuvant intravitreal ranibizumab treatment in high-risk ocular melanoma patients: a two-stage single-centre phase II single-arm study
Despite an established history of intraocular antivascular endothelial growth factor (anti-VEGF) agents therapy in a variety of ocular pathologies as well as other cancer forms, use in the primary treatment of uveal melanoma has not been well assessed. This was a two-stage therapeutic and exploratory phase II, non-randomised, single centre trial involving intraocular treatment with 0.5 mg in 0.05 ml of ranibizumab via six intravitreous injections over 6 months in patients with primary ocular melanoma that otherwise required radical surgery because of tumour size. Seven patients were recruited with a median age of 66 years....
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Short Communications Source Type: research
The programmed cell death protein-1/programmed cell death ligand 1 expression, CD3+ T cell infiltration, NY-ESO-1 expression, and microsatellite instability phenotype in primary cutaneous melanoma and mucosal melanoma and their clinical significance and prognostic value: a study of 89 consecutive cases
We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), and NY-ESO-1 antigen; the infiltration of CD3+ T cells; and the microsatellite instability (MSI) phenotype, as well as the relationship of each factor to survival in malignant melanoma patients. Malignant melanoma samples from 89 patients were stained by immunohistochemistry to evaluate PD-1, PD-L1, CD3+ tumor-infiltrating lymphocytes (TILs), NY-ESO-1, and MSI. PD-1 and PD-L1 were expressed in 19.1 and 32.6% of the 89 samples, respectively. There was a significant correlation between PD-1 and PD-L1 expression (râ€...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research
Nivolumab for patients with metastatic uveal melanoma previously untreated with ipilimumab: a single-institution retrospective study
The objective response and disease control rates were 7.1% and 42.9%, respectively (one partial response and five stable diseases). The median progression-free survival and overall survival were 10 (range, 4–105) and 60 (range, 5–105) weeks, respectively. Liver metastases in three patients were all programmed cell death-1 ligand negative. Lower lactate dehydrogenase, development of vitiligo, and a neutrophil-to-lymphocyte ratio less than 5 at week 6 were associated with favorable progression-free survival and overall survival; of these, only a neutrophil-to-lymphocyte ratio less than 5 at week 6 was statistically signi...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research
Absolute lymphocyte count as a prognostic biomarker for overall survival in patients with advanced melanoma treated with ipilimumab
Biomarkers are needed to estimate which patients benefit most from combination ipilimumab and nivolumab immunotherapy. Rigorous biomarker analyses from prior ipilimumab randomized studies without nivolumab are likely to inform which biomarker analyses should be prioritized when examining patients treated with the combination. For the first time, the current analyses investigate absolute lymphocyte count (ALC) in randomized, controlled trials of ipilimumab without nivolumab to assess whether ALC is prognostic or predictive of ipilimumab treatment benefit. Data included patients (n = 1136) treated in the two randomized, cont...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research
Frequency of mutations in BRAF, NRAS, and KIT in different populations and histological subtypes of melanoma: a systemic review
The presence of mutations of BRAF, NRAS, and KIT genes is recognized as playing a role during carcinogenesis. Our study aims to evaluate and review other studies that present the frequency of mutations of BRAF, NRAS, and KIT genes for different populations, and analyse correlation to their clinical-pathological characteristics and to the demographics of melanoma. Thirty-two articles were selected from a collection of published literature studying 6299 patients. The parameters for correlation to different variables were calculated by odds ratio, for random and single effects. 38.5% of patients present BRAF gene mutations, 1...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research
Enrichment of melanoma-associated T cells in 6-thioguanine-resistant T cells from metastatic melanoma patients
This study examines whether 6-thioguanine resistant T cells (mutant) from metastatic melanoma patients are enriched for melanoma-associated T cells compared to T cells obtained analogously without thioguanine selection (wild-type). Melanoma-associated antigen pentamer staining was performed on 5 tumour and 9 peripheral blood samples from metastatic melanoma patients. T cell receptor beta chain repertoire was examined via Sanger sequencing of mutant and wild-type in blood and tumour from metastatic melanoma patients at times of tumour progression (n = 8) and via Illumina sequencing in tumour derived T cells and in unculture...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research
Anti-angiogenic effects of mangiferin and mechanism of action in metastatic melanoma
In this study, we demonstrate that mangiferin interferes with inflammation, lipid and calcium signaling which selectively inhibits multiple NFkB target genes including interleukin-6, tumor necrosis factor, interferon gamma, vascular endothelial growth factor receptor 2, plasminogen activator urokinase, matrix metalloprotease 19, C-C Motif Chemokine Ligand 2 and placental growth factor. This abrogates angiogenic and invasive processes and capillary tube formation of metastatic melanoma cells as well as human placental blood vessel explants in-vitro and blocks angiogenesis characteristic of the chicken egg chorioallantoic me...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research
Identification of robust reference genes for studies of gene expression in FFPE melanoma samples and melanoma cell lines
There is an urgent need for novel diagnostic melanoma biomarkers that can predict increased risk of metastasis at an early stage. Relative quantification of gene expression is the preferred method for quantitative validation of potential biomarkers. However, this approach relies on robust tissue-specific reference genes. In the melanoma field, this has been an obstacle due to lack of validated reference genes. Accordingly, we aimed to identify robust reference genes for normalization of gene expression in melanoma. The robustness of 24 candidate reference genes was evaluated across 80 formalin-fixed paraffin-embedded melan...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research
CXCR4 inhibition modulates the tumor microenvironment and retards the growth of B16-OVA melanoma and Renca tumors
To determine whether blockade of the chemokine receptor CXCR4 might alter the tumor microenvironment and inhibit tumor growth, we tested the efficacy of the CXCR4 antagonist X4-136 as a single agent and in combination with various immune checkpoint inhibitors in the syngeneic murine melanoma model B16-OVA. We also tested its activity alone and in combination with axitinib in the renal cancer model Renca. We found that X4-136 exhibited potent single agent antitumor activity in the B16-OVA model that was additive to that of an anti-PDL1 antibody. The antitumor activities were associated with a reduction in the number of immu...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research
Exploring metabolic reprogramming in melanoma via acquired resistance to the oxidative phosphorylation inhibitor phenformin
Therapeutic failures in cancer therapy are often associated with metabolic plasticity. The use of metabolic modulators as anti-cancer agents has been effective in correcting metabolic alterations; however, molecular events behind metabolic switch are still largely unexplored. Herein, we characterize the molecular and functional events that follow prolonged oxidative phosphorylation inhibition by phenformin in order to study how melanoma cells adapt to this specific metabolic pressure. We show that melanoma cells cultured up to 3 months with high doses of phenformin (R-cells) are less viable and migrate and invade less than...
Source: Melanoma Research - January 3, 2020 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research
Decreased vitamin D serum levels at melanoma diagnosis are associated with tumor ulceration and high tumor mitotic rate
The aim of this study is to evaluate the relation between 25-hydroxyvitamin D levels at diagnosis and pathological characteristics in primary invasive melanoma. A cross-sectional study was designed based on a series of 204 consecutive patients diagnosed of invasive melanomas in the 2013–2017 period at a single institution. 25-hydroxyvitamin D serum levels at diagnosis were assessed, and three groups were defined by vitamin D status: deficiency, insufficiency, and sufficiency. Clinical and pathological characteristics were compared between the groups by Chi-square test. Logistic regression models were performed to evaluat...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Short Communications Source Type: research
Lack of association of metastasis-associated lung adenocarcinoma transcript 1 variants with melanoma skin cancer risk
In conclusion, our results suggest that there is no contribution of MALAT1 rs3200401 and rs619586 polymorphisms or polymorphisms in the core promoter that could be associated with the risk of melanoma skin cancer in this specific study setting. Further validation will be required in larger studies involving different settings/larger populations in order to reach conclusive results. (Source: Melanoma Research)
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Short Communications Source Type: research
MRI enables accurate diagnosis and follow-up in uveal melanoma patients after vitrectomy
Uveal melanoma (UM), the most common primary intraocular tumour, is often complicated by exudative retinal detachment (RD). Sometimes, this exudative RD is mistaken for a rhegmatogenous detachment and is subsequently treated with vitrectomy with silicone oil (SiOil) tamponade. As SiOil prevents ultrasound imaging, the diagnosis, treatment planning and/or follow-up of UM underlying the detachment are often severely hindered by the SiOil. We aim to develop and evaluate new MRI methods to image UM patients with a SiOil tamponade and evaluate this in vivo. A dedicated MRI protocol for 3 and 7 T was developed and subsequently e...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Short Communications Source Type: research
Single-center real-life experience with low-dose ipilimumab monotherapy in adjuvant setting for patients with stage III melanoma
Ipilimumab is approved for adjuvant melanoma treatment at a dose of 10 mg/kg, but its use is limited owing to high toxicity and treatment-associated costs. We retrospectively analyzed 29 patients who underwent complete resection of stage IIC–III melanoma and were treated with ipilimumab 3 mg/kg in an adjuvant setting. The aim was to assess development of adverse events (primary endpoint) and to evaluate survival outcomes (secondary endpoint) under adjuvant treatment with ipilimumab in a real-life setting. Immune-related adverse events (irAE) of all grades were reported in 72.4% of patients, grade 3 in 5.3% (n = 2), and n...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research
Exceptional responses with sequential metronomic temozolomide after pembrolizumab failure in patients with metastatic melanoma
Pembrolizumab is an effective therapy for patients with metastatic melanoma. However, not all patients derive benefit. It is postulated that an increase in regulatory T cells in melanoma patients can impair the response to immunotherapies. Continuous low-dose temozolomide has shown to cause immunomodulatory effects resulting in CD4 + lymphopenia due to which Treg population can also decrease significantly. Herein, we present a case series of three patients with metastatic melanoma who after progression on pembrolizumab showed a radiological response after just one cycle of metronomic temozolomide (75 mg/m2 daily for 6 week...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research
