A population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma
Ipilimumab is an anti-CTLA4 monoclonal antibody with demonstrated efficacy for metastatic melanoma in randomized controlled trials, including in the first-line setting. Population-based outcomes directly compared with historic chemotherapy treatment in metastatic or unresectable melanoma are lacking. Using population-based data from the province of Ontario, the benefit of first-line ipilimumab was estimated by comparing outcomes of patients treated with first-line dacarbazine over the period 2007–2009 with patients treated over the period 2010–2015 with first-line ipilimumab. Cutaneous and noncutaneous cases were inclu...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research
Immunotargeted therapy in melanoma: patient, provider preferences, and willingness to pay at an academic cancer center
New melanoma therapies have shifted the expectations of patients and providers. Evaluating the impact of treatment characteristics may enhance shared decision making. A survey, including a discrete choice experiment, was utilized to evaluate perceived trade-offs of different melanoma treatments and to estimate out-of-pocket (OOP) willingness-to-pay (WTP) thresholds (January 2016 to March 2016). Participants included patients with melanoma at Huntsman Cancer Institute and their cancer care providers. Stakeholder focus groups were conducted to identify treatment attributes. Descriptive and comparative statistics and multinom...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research
Correlation of serum tryptase levels with total number of nevi, Breslow thickness, ulceration, and mitotic index in melanoma patients: evaluation of a promising prognostic marker
Current evidences suggest that mast cells contribute to the proliferation and differentiation of skin melanocytes. According to these findings, we carried out an observational cross-sectional study to investigate the correlation between the total number of nevi (TN), Breslow thickness (BT), and serum tryptase (ST) levels in a cohort of 35 melanoma (MM) patients. A Mann–Whitney test was performed to compare ST values within each variable. Subsequently, the independent predictive factors were assessed by multiple logistic regression. Pearson’s χ2-test was chosen to detect statistically significant findings on the TN and...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Original Articles: Clinical Research Source Type: research
GLT8D1 overexpression as a novel prognostic biomarker in human cutaneous melanoma
Aberrant glycosylation plays a major role in the progression of melanoma, but little is known about glycosyltransferases. Glycosyltransferase 8 domain containing 1 (GLT8D1) is located in the Golgi apparatus and is related to transferase activity in mammals. However, its role in cancer remains unclear. The aim of this study was to investigate the expression of GLT8D1 in human melanoma and explore the relationship between GLT8D1 expression and the clinicopathological characteristics of melanoma patients via GEO data analysis combined with clinical patient data. The analysis of 45 malignant melanoma samples and 18 benign nevu...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research
Diagnostic and prognostic value of glucose transporters in melanocytic lesions
We have previously reported increased glucose transporter 1 (GLUT1) expression in melanoma compared to benign nevi, associated with a significantly lower survival rate. GLUT1 upregulation was highly specific for distinguishing melanoma from benign nevi, yet poorly sensitive, likely because of expression of other GLUT isoforms. The purpose of this study was to evaluate GLUT2 and GLUT3, as melanoma biomarkers. A tissue microarray, consisting of 91 primary melanomas, 18 melanoma metastases, and 56 nevi, was examined using GLUT2 and GLUT3 immunohistochemistry. A semiquantitative scoring method was used to determine the percent...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research
DNMT1 and DNMT3B genetic polymorphisms affect the clinical course and outcome of melanoma patients
The aberrant DNA methylation plays a critical role in a number of different malignancies, including melanoma. DNA methylation is catalyzed by DNA methyltransferases (DNMTs), involved in methylation maintenance (DNMT1) and de novo DNA methylation (DNMT3A and DNMT3B). The current study investigated the association of genetic variants in the DNMT1 and DNMT3B with the clinicopathologic features and the clinical course of melanoma patients. In the present study, DNMT1 (rs2228612, rs2228611, and rs2114724) and DNMT3B (rs406193 and rs2424932) polymorphisms were examined in 123 melanoma patients. Single nucleotide polymorphisms we...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research
Melanoma susceptibility variant rs869330 in the MTAP gene is associated with melanoma outcome
The rising incidence of cutaneous melanoma (CM), an aggressive skin cancer, emphasizes the need for novel biomarkers to guide personalized care and better predict outcome. Genetic factors including germline risk variants are promising candidates for this aim. We explored the association between germline risk variants and melanoma outcome in a large genetically homogenous Belgian melanoma population, focusing on single nucleotide polymorphisms which generated the highest association with melanoma susceptibility. Between 2004 and 2014, blood samples of 1088 patients with histologically confirmed CM were collected and genotyp...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Original Articles: Translational Research Source Type: research
A novel germline variant in the DOT1L gene co-segregating in a Dutch family with a history of melanoma
A proportion of patients diagnosed with melanoma has a positive family history. Despite increasing knowledge on the genes responsible for familial clustering, the genetic basis in the majority of the families with an inherited predisposition to melanoma remains to be clarified. To identify novel melanoma-susceptibility genes, we applied whole-exome sequencing on DNA from two members of a family with four melanoma cases, not explained by established high penetrance melanoma-susceptibility genes. Whole-exome sequencing identified 10 rare, co-segregating, predicted deleterious missense gene variants. Subsequent co-segregation...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research
Long noncoding RNA ZFAS1 promotes tumorigenesis through regulation of miR-150-5p/RAB9A in melanoma
Melanoma is the deadliest form of skin cancer and one of the most aggressive cancers. ZFAS1 is a newly identified lncRNA, playing an oncogenic role in several types of cancer. The present study aimed to investigate the function and mechanism of ZFAS1-induced regulation of melanoma. ZFAS1 expression was increased in melanoma tissues and cells compared with normal controls. ZFAS1 expression in metastatic tissues was higher than that in nonmetastatic subjects. Higher expression of ZFAS1 predicted lower survival rates. Knockdown of ZFAS1 decreased proliferation, increased apoptosis, decreased migration and invasion, and reduce...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Original Articles: Basic Science Source Type: research
Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis
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-reviewed data. The design is a systematic review and meta-analysis. We searched PubMed from 1 January 1980, to 29 March 2017, for articles reporting patient-level survival in Kaplan–Meier or numerical form. We digitized survival graphs, pooled individual survival times, calculated median OS by treatment modality, and compared each modality by the log-rank test and Co...
Source: Melanoma Research - November 4, 2019 Category: Cancer & Oncology Tags: Review Article Source Type: research
Severe gastrointestinal toxicity of MEK inhibitors
Gastrointestinal toxicities of MEK inhibitors in melanoma patients are frequent. In clinical trials, the most common digestive adverse events were nausea, vomiting, and diarrhoea. However, severe toxicities such as colitis and gastrointestinal perforation, some with fatal outcomes, have been reported. These rare but severe adverse events are not well described. We performed a retrospective analysis of all patients with stage IV and unresectable stage III melanoma treated with a MEK inhibitors at Saint-Louis Hospital, Paris, between 1 August 2013 and 15 October 2018. Among 119 patients exposed to MEK inhibitors, 78 were tre...
Source: Melanoma Research - September 3, 2019 Category: Cancer & Oncology Tags: Short Communications: Clinical Research Source Type: research
Are patients in haemodialysis good candidates for immunotherapy treatment?
The effectiveness and safety of nivolumab, an anti-programmed cell death protein 1 mAbmonoclonal antibody, in patients with renal replacement therapy is unclear, with limited evidence supporting its usefulness in this context. Therefore, we report a case of recurrent metastatic melanoma in a patient on haemodialysis successfully treated with nivolumab. As seen in patients without renal impairment, significant regression of the lesions was observed after 8 weeks of treatment, reaching complete clinical response after 4 months. During follow-up, no dose adjustment, delay, or treatment suspension due to toxicity were required...
Source: Melanoma Research - September 3, 2019 Category: Cancer & Oncology Tags: Short Communications: Clinical Research Source Type: research
Immune-related pancreatitis associated with checkpoint blockade in melanoma
We present a patient who developed an immune-related pancreatitis within the first 4 months of immunotherapy. Treatment with high dose systemic glucocorticosteroids with very slow tapering over a total period of 6.5 months was necessary to keep the patient symptom free as well as to maintain long-term normalization of serum lipase. Checkpoint blockade related pancreatitis may occur as acute or chronic disease and may lack any radiographic signs. As in our case, very slow tapering of initially high dose systemic glucocorticosteroids seems to be a crucial requirement for lasting recovery. Even after successful treatment, lat...
Source: Melanoma Research - September 3, 2019 Category: Cancer & Oncology Tags: Short Communications: Clinical Research Source Type: research
Semaphorin-5A downregulation is associated with enhanced migration and invasion of BRAF-positive melanoma cells under vemurafenib treatment in melanomas with heterogeneous BRAF status
Tumor heterogeneity affects the efficacy of anticancer treatment as tumor subclones with distinct molecular patterns may be present within one tumor, leading to differing sensitivities to chemotherapeutic agents. In the present study, six melanoma tissue fragments were obtained from different parts of tumor of four patients and then the effect of vemurafenib treatment on biological characteristics and molecular processes of cell cultures was estimated by using MTT-test, apoptosis, migration and invasion assays, PCR real time. There was different BRAF status determined between cells derived from the central and peripheral r...
Source: Melanoma Research - September 3, 2019 Category: Cancer & Oncology Tags: Short Communications: Basic Science Source Type: research
Protein kinase C-α is upregulated by IMP1 in melanoma and is linked to poor survival
The oncofetal mRNA-binding protein, IMP1 or insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1), promotes the overexpression of several oncogenic proteins by binding to and stabilizing their mRNAs. IMP1 is frequently overexpressed in melanoma and is associated with a poor prognosis, but the full spectrum of IMP1 target transcripts remains unknown. Here, we report the identification of protein kinase C-α (PKCα), as a novel molecular target of IMP1. Overexpression of IMP1 resulted in increased levels of PKCα, while RNAi knockdown of IMP1 resulted in decreased PKCα mRNA stability, PKCα protein levels, and MAPK/...
Source: Melanoma Research - September 3, 2019 Category: Cancer & Oncology Tags: Short Communications: Basic Science Source Type: research
