ASAP Selective PKCd Inhibitor B106 Elicits Uveal Melanoma Growth Inhibitory Effects Independent of Activated PKC Isoforms

ACS Chemical BiologyDOI: 10.1021/acschembio.8b00292
Source: ACS Chemical Biology - Category: Chemistry Authors: Source Type: research

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We examined these patterns with digital image analysis and transmission electron microscopy, and correlated them with BAP-1 expression, gene expression class, macrophage infiltration, and metastatic disease in full tumor cross-sections and intratumor regions. Methods: Thirty-two enucleated eyes with UM were stained immunohistochemically (BAP-1, laminin, CD31, and CD68) and with PAS without hematoxylin counterstain. Retrospective data on gene expression class and patient survival were retrieved. Tumor sections were digitally scanned and analyzed with the QuPath Bioimage analysis software, and imaged with transmission el...
Source: Molecular Vision - Category: Molecular Biology Tags: Mol Vis Source Type: research
ConclusionsCollectively our data suggest that a nonselective beta ‐blocker may be effective against melanoma. For the first time, we show potent anti‐tumor effects in UM cells following propranolol administration and expression of β1 and β2 adrenoceptors in patient tissue.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Kiilgaard Donia Svane Uveal melanoma (UM) is the most common intraocular malignancy in adults and shows a high rate of metastatic spread. As randomized clinical trials with immune checkpoint inhibitors (ICI) have not been performed in patients with metastatic UM, we analyzed the real-world outcomes in a nationwide population-based study. Clinical data of patients with UM were extracted from the Danish Metastatic Melanoma database, a nationwide database containing unselected records of patients diagnosed with metastatic melanoma in Denmark. Survival before (pre-ICI, n = 32) and after (post-ICI, n = 94) the appro...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
AbstractBackgroundUveal melanoma (UM) is a rare cancer that arises from melanocytes in the uveal tract of the eye. Despite effective treatment for primary UM,> 50% of patients develop metastatic disease. There is currently no effective treatment for metastatic UM and median life expectancy is  
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsSelPac met its primary endpoint, demonstrating a statistically significant improvement in PFS for SEL + PT without a significant increase in toxicity. No trend for a prolongation of OS was observed.Clinical trial identificationISRCTN 29621851.Legal entity responsible for the studyUniversity of Liverpool&Liverpool Cancer Trials Unit.FundingCancer Research UK and AstraZeneca.DisclosureP. Nathan: Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: AstraZeneca; Honoraria (self), Advisory / Consultancy, Consultancy / advisory board: BMS; Honoraria (self), Advisory / Consultancy, Consultancy / ...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsThe PEMDAC study has demonstrated that combined HDAC- and PD-1-inhibition can result in clinical efficacy in metastatic uveal melanoma with manageable toxicities. The obtained data warrant further investigation to address clinical and immunological characteristics of patients achieving clinical benefit.Clinical trial identificationNCT02697630 (Registered 3 March 2016). EudraCT: 2016-002114-50.Legal entity responsible for the studySahlgrenska University Hospital, V ästra Götaland Region.FundingSyndax Pharmaceuticals and Merck&Co. Inc.DisclosureR. Olofsson Bagge: Advisory / Consultancy: Merck&Co....
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
ConclusionsTreatment with MART-1 TCR transduced peripheral blood T cells expanded in presence of IL-7 and IL-15 led to severe dose-dependent toxicity with a maximum tolerated dose of 10 x 107 transduced cells. Despite observed responses, toxicity limited further development and use of this MART-1 TCR cellular therapy in MM patients. NCT02654821.Clinical trial identificationNCT02654821.Legal entity responsible for the studyNetherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL).FundingKWF Kankerbestrijding.DisclosureJ.H. Beijnen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Modra Ph...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
In this study, we found that: (a) high expression of lncRNAMIR155 host gene (MIR155HG) was closely related to better overall survival (OS) in cholangiocarcinoma (CHOL), lung adenocarcinoma (LUAD), and skin cutaneous melanoma (SKCM), and have better disease ‐free survival (DFS) in CHOL. Meanwhile, the high level ofMIR155HG was associated with poorer OS in glioblastoma multiforme (GBM), kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and uveal melanoma (UVM). (b) The expression ofMIR155HG was significantly correlated with infiltrating levels of immune cells and immune molecules, especially with im...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
Publication date: Available online 26 September 2019Source: Progress in Retinal and Eye ResearchAuthor(s): Kyra N. Smit, Martine J. Jager, Annelies de Klein, Emine KiliҫAbstractUveal melanoma is an aggressive malignancy that originates from melanocytes in the eye. Even if the primary tumor has been successfully treated with radiation or surgery, up to half of all UM patients will eventually develop metastatic disease. Despite the common origin from neural crest-derived cells, uveal and cutaneous melanoma have few overlapping genetic signatures and uveal melanoma has been shown to have a lower mutational burden. As a conse...
Source: Progress in Retinal and Eye Research - Category: Opthalmology Source Type: research
Abstract MITF, a gene that is mutated in familial melanoma and Waardenburg syndrome, encodes multiple isoforms expressed from alternative promoters that share common coding exons but have unique amino termini. It is not completely understood how these isoforms influence pigmentation in different tissues and how expression of these independent isoforms of MITF are regulated. Here, we show that melanocytes express two isoforms of MITF, MITF-A and MITF-M. Expression of MITF-A is partially regulated by a newly identified retinoid enhancer element located upstream of the MITF-A promoter. Mitf-A knockout mice have only ...
Source: Pigment Cell and Melanoma Research - Category: Cytology Authors: Tags: Pigment Cell Melanoma Res Source Type: research
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