Tris DBA palladium is an orally available inhibitor of GNAQ mutant uveal melanoma in vivo.

Tris DBA palladium is an orally available inhibitor of GNAQ mutant uveal melanoma in vivo. Oncotarget. 2019 Jul 08;10(43):4424-4436 Authors: Musi E, Schwartz GK, Yoo JH, Odelberg SJ, Li DY, Bonner MY, Selvakumar P, Rao S, Gilbert LC, Elsey J, Arbiser JL Abstract Uveal melanoma is a rare but often lethal malignancy and is the leading cause of death due to an ophthalmic condition. Uveal melanoma is often diagnosed at a late stage and has a strong propensity to hepatic metastasis. Recently, the most common driver mutations in uveal melanoma have been identified, predominantly in the G-proteins GNAQ. This pattern differs from that of cutaneous melanoma in which Braf and Nras predominate. There are no current clinically used agents that target GNAQ mutations, unlike the use of Braf inhibitors in cutaneous melanoma. We tested the novel agent Tris DBA palladium and found that it was markedly more effective against GNAQ mutant melanomas than wild type uveal melanomas. Given that ARF6 has recently been discovered as a node in GNAQ mutations, we evaluated the efficacy of Tris DBA palladium on ARF6 signaling and found that it was effective in inhibiting ARF6 activation. Finally, Tris DBA palladium was orally effective against GNAQ mutant melanoma in vivo. Tris DBA Palladium deserves further evaluation as a systemic agent for uveal melanoma. PMID: 31320995 [PubMed]
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Related Links:

Conclusions: Whereas in myelodysplastic syndrome predominantly missense SRSF2 mutations are described, the observed SRSF2 mutations in UM are all in-frame deletions of 8–9 amino acids. This suggests that the R625 missense SF3B1 mutations and SRSF2 mutations in UM are different compared to the spliceosome gene mutations in hematological cancers, and probably target a different, as yet unknown, set of genes involved in uveal melanoma etiology.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Communication Source Type: research
Conclusions: The results indicate that patients with nevus of Ota should undergo regular ophthalmological observation and be aware of the potential for malignancy. PMID: 31407624 [PubMed - as supplied by publisher]
Source: Ophthalmic Genetics - Category: Opthalmology Tags: Ophthalmic Genet Source Type: research
Authors: Lamagna B, Uccello V, Prisco F, Russo V, Lamagna F, Navas L, Mennonna G, Murino C, Meomartino L Abstract A 13-year-old Domestic Shorthair female cat, with a history of phthisis bulbi of the right eye, was referred for an acute increase in the size of the right ocular globe that occurred over a period of 1 month. Ocular examination revealed a large pink/greyish neoplastic mass involving the entire ocular surface. Ocular ultrasound and cytological examination confirmed intraocular tumor of the phthisical eye extending into the cranial space of the right orbit. The diagnosis of a primary, poorly pigmented iri...
Source: Veterinary Quarterly - Category: Veterinary Research Tags: Vet Q Source Type: research
This study compared the cytogenetic profiles of choroidal melanoma samples retrieved before and after proton beam irradiation. Twenty-four consecutive patients who underwent both fine-needle aspiration biopsy (FNAB) during tantalum clip positioning, and endoresection within three months of irradiation, were retrospectively included. Chromosome alterations were explored by array comparative genomic hybridization. Age at diagnosis was 50 ± 14 years, tumor thickness was 8.6 ± 1.7 mm and tumor diameter was 12.4 ± 2.3 mm. Six FNAB samples were non-contributive (25%), versus one endoresection sam...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
CONCLUSIONS: A nomogram using clinical or treatment risk factors can predict visual acuity outcome following plaque radiotherapy and prophylactic intravitreal bevacizumab for uveal melanoma and is available online at PMID: 31409650 [PubMed - as supplied by publisher]
Source: The British Journal of Ophthalmology - Category: Opthalmology Authors: Tags: Br J Ophthalmol Source Type: research
Reactivation of functionally-impaired anticancer T cells by programmed cell death protein 1 (PD-1) and programmed cell death receptor ligand-1 (PD-L1) –blocking antibodies shows prominent therapeutic benefit in advanced melanoma and patients with non–small cell lung cancer. However, current PD-L1–blocking antibodies lack intrinsic tumor selectivity. Therefore, efficacy may be reduced resulting from on-target and off-tumor binding to PD-L1– expressing normal cells. This may lead to indiscriminate activation of antigen-experienced T cells, including those implicated in autoimmune-related adverse events.
Source: Journal of Investigative Dermatology - Category: Dermatology Authors: Tags: Original Article Source Type: research
n Jager Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, and gives rise to metastases in 50% of cases. The presence of an inflammatory phenotype is a well-known risk factor for the development of metastases. This inflammatory phenotype is characterized by the presence of high numbers of lymphocytes and macrophages, and a high expression of the HLA Class I and II antigens. An abnormal expression of HLA Class I may influence cytotoxic T lymphocyte (CTL) as well as Natural Killer (NK) cell responses. We provide a comprehensive review regarding the inflammatory phenotype in UM and the exp...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Martine J. Jager Inflammation, characterized by high numbers of infiltrating leukocytes and a high HLA Class I expression, is associated with a bad prognosis in uveal melanoma (UM). We wondered whether mutations in GNA11 or GNAQ differentially affect inflammation and HLA expression, and thereby progression of the disease. We analyzed data of 59 primarily enucleated UM eyes. The type of GNAQ/11 mutation was analyzed using dPCR; chromosome aberrations were determined by Fluorescence in Situ Hybridization (FISH), karyotyping, and single nucleotide polymorphism (SNP) analysis, and mRNA expression by Illumina PCR. Comparin...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
. Kiilgaard Ruthenium-106 (Ru-106) brachytherapy is an established modality for eye-preserving treatment of choroidal melanoma. To achieve optimal treatment outcomes, there should be a balance between tumour control and the risk of healthy tissue toxicity. In this retrospective study, we examined normal tissue complication probability (NTCP) for visual acuity deterioration and late complications to aid the understanding of dose-dependence after Ru-106 treatments. We considered consecutive patients diagnosed with choroidal melanoma and primarily treated at a single institution from 2005–2014. Treatment plans w...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
In this study, we showed PI3K/Akt/MMP9 pathway activity could be positively regulated by HMGA1 using western blotting, real-time polymerase chain reaction (RT-PCR) and immunochemistry both in vitro (C918 and MUM-2B cell lines) and in vivo (xenograft mouse model). Later, MiRTarBase was used to identify the relationship between HMGA1 and miR-222-3p, we found miR-222 is positively regulated by HMGA1. Moreover, the proliferation and migration of UM cells significantly increased in the miR-222 mimics group and decreased in the miR-222 inhibitor group detected by the Annexin V-FITC apoptosis detection kit, CCK-8 and scratch woun...
Source: Cellular Signalling - Category: Cytology Authors: Tags: Cell Signal Source Type: research
More News: Cancer & Oncology | Eye Cancers | Melanoma | Opthalmology | Skin Cancer | Uveal Melanoma