scholarly journals The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma

Oncotarget ◽  
2020 ◽  
Vol 11 (2) ◽  
pp. 175-187 ◽  
Author(s):  
Klara Fodor ◽  
Nikoletta Dobos ◽  
Andrew Schally ◽  
Zita Steiber ◽  
Gabor Olah ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Expression Of Genes ◽  
Lhrh Analog

scholarly journals Increased Non-Homologous End Joining Makes DNA-PK a Promising Target for Therapeutic Intervention in Uveal Melanoma

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1278 ◽  
Author(s):  
Doherty ◽  
Bryant ◽  
Valluru ◽  
Rennie ◽  
Sisley
Keyword(s):  
Uveal Melanoma ◽  
Messenger Rna ◽  
Therapeutic Option ◽  
Survival Rates ◽  
The Cancer Genome Atlas ◽  
End Joining ◽  
Expression Of Genes ◽  
Effective Therapeutic Option ◽  
Non Homologous End Joining ◽  
Induced Apoptosis

Uveal melanoma (UM) is the most common primary intraocular tumour in adults, with a mean survival of six months following metastasis. The survival rates have not improved in over 30 years. This study has shown that sister chromatid exchange (SCE) is low in UM which is likely due to a reduced expression of FANCD2. As FANCD2 can function to suppress non-homologous end joining (NHEJ), this study therefore investigated NHEJ in UM. The activation of the catalytic subunit of the NHEJ pathway protein DNA-dependent protein kinase (DNA-PK) was measured by analysing the foci formation and the ligation efficiency by NHEJ determined using a plasmid-based end-joining assay. Using small-interfering RNA (siRNA) knock-down, and chemical inhibitors of DNA-PK, the survival of primary UM cultures and two cell lines were determined. To assess the homologous recombination capacity in response to the inhibition of DNA-PK, a SCE analysis was performed. In addition, to support the findings, the messenger RNA (mRNA) expression of genes associated with NHEJ was analysed using the Cancer Genome Atlas (TCGA)-UM RNAseq data (n = 79). The NHEJ activity and DNA-PKcs activation was upregulated in UM and the inhibition of DNA-PK selectively induced apoptosis and sensitized to ionising radiation and inter-strand cross-linking agents. The inhibition of the NHEJ protein DNA-PK is lethal to UM, indicating a potentially effective therapeutic option, either alone or as a sensitizer for other treatments.

scholarly journals Aberrant MicroRNA Expression and Its Implications for Uveal Melanoma Metastasis

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 815 ◽  
Author(s):  
Kyra N. Smit ◽  
Jiang Chang ◽  
Kasper Derks ◽  
Jolanda Vaarwater ◽  
Tom Brands ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Target Genes ◽  
Microrna Expression ◽  
Differentially Expressed ◽  
Melanoma Metastasis ◽  
Genetic Changes ◽  
Expression Of Genes ◽  
Aggressive Cancer ◽  
Metastatic Risk ◽  
Egf Signaling

Uveal melanoma (UM) is the most frequently found primary intra-ocular tumor in adults. It is a highly aggressive cancer that causes metastasis-related mortality in up to half of the patients. Many independent studies have reported somatic genetic changes associated with high metastatic risk, such as monosomy of chromosome 3 and mutations in BAP1. Still, the mechanisms that drive metastatic spread are largely unknown. This study aimed to elucidate the potential role of microRNAs in the metastasis of UM. Using a next-generation sequencing approach in 26 UM samples we identified thirteen differentially expressed microRNAs between high-risk UM and low/intermediate-risk UM, including the known oncomirs microRNA-17-5p, microRNA-21-5p, and miR-151a-3p. Integration of the differentially expressed microRNAs with expression data of predicted target genes revealed 106 genes likely to be affected by aberrant microRNA expression. These genes were involved in pathways such as cell cycle regulation, EGF signaling and EIF2 signaling. Our findings demonstrate that aberrant microRNA expression in UM may affect the expression of genes in a variety of cancer-related pathways. This implies that some microRNAs can be responsible for UM metastasis and are promising potential targets for future treatment.

scholarly journals Imatinib Mesylate Alters the Expression of Genes Related to Disease Progression in an Animal Model of Uveal Melanoma

2011 ◽  
Vol 34 (3) ◽  
pp. 123-130 ◽  
Author(s):  
Bruno F. Fernandes ◽  
Sebastian Di Cesare ◽  
Rubens Neto Belfort ◽  
Shawn Maloney ◽  
Claudia Martins ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Uveal Melanoma ◽  
Metastatic Disease ◽  
Treated Group ◽  
Suppressor Gene ◽  
Control Group ◽  
Metastasis Suppressor ◽  
Pcr Array ◽  
Intraocular Tumors ◽  
Expression Of Genes

Imatinib mesylate (IM) is a compound that inhibits both BCR-ABL tyrosine kinase and c-kit receptors. Tyrosine kinases are important in cellular signaling and mediate major cellular processes such as proliferation, differentiation, apoptosis, attachment, and migration. Twenty-six albino rabbits were injected with 1 × 106 human uveal melanoma (UM) cells (92.1) into the suprachoroidal space. Animals were immunosuppressed (cyclosporin A) over the course of the 12-week experiment and divided into two groups (n = 13). The experimental group received IM once daily by gavage while the control group received a placebo. One animal per group was sacrificed every week after the 2nd week. Upon necropsy, organs were harvested for histopathological examination. Cells from the primary tumors were recultured and tested in proliferation and invasion assays. A PCR array was used to investigate the differences in expression of 84 genes related to tumor metastasis. In the treated group, 4 rabbits developed intraocular tumors, with an average largest tumor dimension (LTD) of 2.5 mm and 5 animals reported metastatic disease. Whereas 6 rabbits in the control group developed intraocular tumors, with an average LTD of 5.8 mm and 6 animals reported metastatic disease. The recultured cells from the treated group demonstrated lower proliferation rates and were less invasive (p < 0.001 The PCR array showed differences in expression of genes related to metastasis. Notably, there was 290-fold increase inSERPINB5, a tumor suppressor gene, and a 10-fold higher expression ofKISS1, a metastasis suppressor gene, in the treated group. Proangiogenic genes such asVEGFA,PDGFAandPDGFBwere downregulated in the treated group. To the best of our knowledge, this is the first report detailing the altered expression of specific genes in UM cells after treatment with IM.

609: Effects of Sirna and Phytoestrogen Treatments on the Expression of Genes Regulated through the Androgen Receptor of Lncap Prostate Cancer Cells

2004 ◽  
Vol 171 (4S) ◽  
pp. 162-162
Author(s):  
Paul Thelen ◽  
Michal Grzmil ◽  
Iris E. Eder ◽  
Barbara Spengler ◽  
Peter Burfeind ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Expression Of Genes

Abstract #1010: Uveal Melanoma Masquerading as A Nontoxic Multinodular Goiter

2015 ◽  
Vol 21 ◽  
pp. 194-195
Author(s):  
Rokshana Thanadar ◽  
Uzma Siddiqui ◽  
Marie Lithgow ◽  
Runhua Hou
Keyword(s):  
Uveal Melanoma ◽  
Multinodular Goiter

Anti-Diabetic Activity of a Mineraloid Isolate, in vitro and in Genetically Diabetic Mice

2011 ◽  
Vol 81 (1) ◽  
pp. 34-42 ◽  
Author(s):  
Joel Deneau ◽  
Taufeeq Ahmed ◽  
Roger Blotsky ◽  
Krzysztof Bojanowski
Keyword(s):  
Dna Microarrays ◽  
Human Fibroblasts ◽  
Diabetic Animal ◽  
In Vitro Tests ◽  
Diabetic Mice ◽  
Fossil Material ◽  
Expression Of Genes ◽  
Enhanced Expression ◽  
Genetically Diabetic Mice

Type II diabetes is a metabolic disease mediated through multiple molecular pathways. Here, we report anti-diabetic effect of a standardized isolate from a fossil material - a mineraloid leonardite - in in vitro tests and in genetically diabetic mice. The mineraloid isolate stimulated mitochondrial metabolism in human fibroblasts and this stimulation correlated with enhanced expression of genes coding for mitochondrial proteins such as ATP synthases and ribosomal protein precursors, as measured by DNA microarrays. In the diabetic animal model, consumption of the Totala isolate resulted in decreased weight gain, blood glucose, and glycated hemoglobin. To our best knowledge, this is the first description ever of a fossil material having anti-diabetic activity in pre-clinical models.

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