'Christmas berry' plant compound could fight Uveal melanoma

(Thomas Jefferson University) A molecule derived from a type of primrose could prove to be a potent inhibitor of metastatic growth for a rare and aggressive cancer.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news

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Direct targeting of Gαq and Gα11 oncoproteins in cancer cells. Sci Signal. 2019 Mar 19;12(573): Authors: Annala S, Feng X, Shridhar N, Eryilmaz F, Patt J, Yang J, Pfeil EM, Cervantes-Villagrana RD, Inoue A, Häberlein F, Slodczyk T, Reher R, Kehraus S, Monteleone S, Schrage R, Heycke N, Rick U, Engel S, Pfeifer A, Kolb P, König G, Bünemann M, Tüting T, Vázquez-Prado J, Gutkind JS, Gaffal E, Kostenis E Abstract Somatic gain-of-function mutations of GNAQ and GNA11, which encode α subunits of heterotrimeric Gαq/11 proteins, occur in about 85% of cases of ...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research
Somatic gain-of-function mutations of GNAQ and GNA11, which encode α subunits of heterotrimeric Gαq/11 proteins, occur in about 85% of cases of uveal melanoma (UM), the most common cancer of the adult eye. Molecular therapies to directly target these oncoproteins are lacking, and current treatment options rely on radiation, surgery, or inhibition of effector molecules downstream of these G proteins. A hallmark feature of oncogenic Gαq/11 proteins is their reduced intrinsic rate of hydrolysis of guanosine triphosphate (GTP), which results in their accumulation in the GTP-bound, active state. Here, we repor...
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Research Articles Source Type: news
Contributors : Grazia Ambrosini ; Catherine Do ; Benjamin Tycko ; Ronald B Realubit ; Charles Karan ; Elgilda Musi ; Richard D Carvajal ; Vivian Chua ; Andrew E Aplin ; Gary K SchwartzSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensBromodomain and extra terminal protein inhibitors (BETi) are epigenetic therapies aimed to target dysregulated gene expression in cancer cells. Despite early success of BETi in a range of malignancies, the development of drug resistance may limit their clinical application. We evaluated the mechanisms of BETi resistance in uveal melanoma (UM), a disease wit...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
. Beenakker Uveal Melanoma (UM) is the most common primary malignant ocular tumor. The high soft tissue contrast and spatial resolution, and the possibility of generating 3D volumetric and functional images, make Magnetic Resonance Imaging (MRI) a valuable diagnostic imaging technique in UM. Current clinical MRI protocols, however, are not optimized for UM and therefore lack the quality for accurate assessments. We therefore developed a dedicated protocol at a 3 Tesla MRI, using an eye coil, consisting of multi-slice 2D sequences, different isotropic sequences and diffusion and perfusion-weighted images. This protocol ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ger Malignant melanoma is the most aggressive and treatment resistant type of skin cancer. It is characterized by continuously rising incidence and high mortality rate due to its high metastatic potential. Various types of cell adhesion molecules have been implicated in tumor progression in melanoma. One of these, the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), is a multi-functional receptor protein potentially expressed in epithelia, endothelia, and leukocytes. CEACAM1 often appears in four isoforms differing in the length of their extracellular and intracellular domains. Both the CEACAM1 expr...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Authors: Falzone L, Romano GL, Salemi R, Bucolo C, Tomasello B, Lupo G, Anfuso CD, Spandidos DA, Libra M, Candido S Abstract Uveal melanoma (UM) represents the most frequent primary tumor of the eye. Despite the development of new drugs and screening programs, the prognosis of patients with UM remains poor and no effective prognostic biomarkers are yet able to identify high‑risk patients. Therefore, in the present study, microRNA (miRNA or miR) expression data, contained in the TCGA UM (UVM) database, were analyzed in order to identify a set of miRNAs with prognostic significance to be used as biomarkers in clini...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
AbstractBalancing the potential for durable remissions with autoimmune-like toxicities is a key clinical challenge in the use of immune checkpoint inhibitors (ICI). Certain toxicities are associated with an increased response rate; however, the molecular underpinnings of this association are poorly understood. Here, we report a patient with wide spread uveal melanoma who had an exceptional response to treatment with ipilimumab and nivolumab, but suffered severe immune-related sequelae, including central serous retinopathy with retinal detachment, tinnitus, and vitiligo resembling Vogt-Koyanagi-Harada disease, and refractor...
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Conclusions: Anti-PD-1-based therapy may cause clinical benefit in metastatic UM, seemingly more often in patients without bulky liver metastases. Lack of mutation burden and T-cell infiltration and MYC overexpression may be factors limiting therapeutic responses.ClinicalTrials.gov identifier: NCT02359851. PMID: 30787124 [PubMed - in process]
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
AbstractPurpose of ReviewInterleukin-10 (IL-10) is a cytokine with anti-inflammatory properties, which induces activation and proliferation of antigen-activated intratumoral CD8+ T cells. This review discusses the evolution of pegylated IL-10 (pegilodecakin) from preclinical investigation through first-in-human studies in oncology.Recent FindingsPegilodecakin was evaluated across multiple advanced solid tumors in a large phase 1/1b trial alone and in combination with chemotherapy or anti-PD-1 antibodies. Pegilodecakin monotherapy had immunologic and clinical activity in renal cell carcinoma (RCC) and uveal melanoma. In com...
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research
In this study, the expression levels of KIF15 in melanoma cells lines and tissues were determined via real-time PCR, immunohistochemical staining and western blot. The effect of KIF15 on tumorigenesis was evaluated by using MTT and colony information. The function of KIF15 on cell survival was detected through flow cytometry assay. Microarray assay and bioinformatics analysis were used to find the potential target of KIF15. We show that KIF15 was significantly upregulated in melanoma cells and tissues. The suppression of KIF15 in tumors significantly reduced tumor growth and increased apoptosis in A375 and OCM1 cells. Find...
Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research
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