Identification of novel chemotherapeutic strategies for metastatic uveal melanoma

Abstract

Melanoma of the uveal tract accounts for approximately 5% of all melanomas and represents the most common primary intraocular malignancy. Despite improvements in diagnosis and more effective local therapies for primary cancer, the rate of metastatic death has not changed in the past forty years. In the present study, we made use of bioinformatics to analyze the data obtained from three public available microarray datasets on uveal melanoma in an attempt to identify novel putative chemotherapeutic options for the liver metastatic disease. We have first carried out a meta-analysis of publicly available whole-genome datasets, that included data from 132 patients, comparing metastatic vs. non metastatic uveal melanomas, in order to identify the most relevant genes characterizing the spreading of tumor to the liver. Subsequently, the L1000CDS2 web-based utility was used to predict small molecules and drugs targeting the metastatic uveal melanoma gene signature. The most promising drugs were found to be Cinnarizine, an anti-histaminic drug used for motion sickness, Digitoxigenin, a precursor of cardiac glycosides, and Clofazimine, a fat-soluble iminophenazine used in leprosy. In vitro and in vivo validation studies will be needed to confirm the efficacy of these molecules for the prevention and treatment of metastatic uveal melanoma.

Transcriptomic analysis reveals moderate modulation of macrophage migration inhibitory factor superfamily genes in alcohol use disorders

“…In addition, we also evaluated the transcriptomic analysis of MIF, DDT and their receptors in the brains of a mouse model of alcoholism. This analysis was carried out by DNA microarray analysis that represents a useful in silico toll for the better understanding of pathogenic pathways and the possible prediction of new diagnostic therapeutic approaches in several clinical settings, including immunoinflammatory and autoimmune diseases and fibrotic diseases (45,46,(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59). Our analysis first demonstrated that no differences in the expression of MIF, DDT and their receptors can be found in brains of both rodent models of AUD and patients with this condition.…”

Analysis of circular RNA‑associated competing endogenous RNA network in breast cancer

“…pathways and therapeutic targets in several diseases, including cancer and autoimmune, fibrotic, neurodegenerative and infectious diseases (22,23,(54)(55)(56)(57)(58)(59). Presti et al (22) utilized RNA-seq data of 281 and 283 DNA-sequenced glioblastoma multiforme and low-grade glioma patients, respectively, to evaluate the expression levels of migration inhibitory factor (MIF) and related genes in glioma.…”

In Silico and In Vivo Analysis of IL37 in Multiple Sclerosis Reveals Its Probable Homeostatic Role on the Clinical Activity, Disability, and Treatment with Fingolimod

“…In the present study, we first analyzed the expression levels of IL37, SIGIRR, and IL18R1 in circulating immune cells from MS patients. In particular, we performed a DNA microarray analysis that represents a useful in silico tool for the better understanding of pathogenic pathways and the possible prediction of novel diagnostic therapeutic strategies, as it has been shown in a variety of clinical settings, such as autoimmune and immunoinflammatory diseases [38][39][40][41][42][43][44] and cancer [45][46][47][48][49][50][51], leading to the identification of novel therapeutic targets [52][53][54][55].…”