In uveal melanoma (UM) cells, the protein kinase C (pathway) is almost generally constitutively activated as a result of an activating mutation in either the GNAQ or the GNA11 G-protein. A pan-PKC inhibitor, sotrastaurin (also named AEB071), is in clinical trials for treatment of UM patients with limited success and eliciting adverse effects. Interestingly, genetic interference with expression of just one PKC isoform, e.g., PKCδ, is sufficient to reduce UM cell proliferation. Therefore, we tested the effect of a recently described specific PKCδ inhibitor, B106, on growth and survival of UM cell lines. Surprisingly, we found that B106 efficiently induced apoptosis in several cell lines, but apparently independent of activated PKCδ.
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http://dx.doi.org/10.1021/acschembio.8b00292 | DOI Listing |
Blood
January 2025
Department I of Internal Medicine and German CLL Study Group; Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD); University of Cologne, Faculty of Medicine and University Hos, Cologne, Germany.
The phase 2 CLL2-BZAG trial tested a measurable residual disease (MRD)-guided combination treatment of zanubrutinib, venetoclax and obinutuzumab after an optional bendamustine debulking in patients with relapsed/refractory CLL. In total, 42 patients were enrolled and two patients with ≤2 induction cycles were excluded from the analysis population per protocol. Patients had a median of one prior therapy (range 1-5), 18 patients (45%) had already received a BTK inhibitor (BTKi), seven patients (17.
View Article and Find Full Text PDFEnviron Sci Technol
January 2025
Key Laboratory of Application of Ecology and Environmental Protection in Plateau Wetland of Sichuan, Xichang University, Xichang 415000 Sichuan Province, China.
This study delves into the adverse effects of AVM, emphasizing oxidative stress induction in the Chinese mitten crab, , and the role of the MAPK-CncC signaling pathway in mediating the antioxidative response. Our findings reveal a dose-dependent impairment in growth performance, alongside occurrence of oxidative stress. The activity of CAT and superoxide dismutase increased significantly in all treatments (0.
View Article and Find Full Text PDFOcul Immunol Inflamm
January 2025
Universiti Malaya Eye Research Centre (UMERC), Department of Ophthalmology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
Purpose: To shed light on one of the ocular adverse effects related to pembrolizumab.
Method: Case report and literature review.
Result: A 53-year-old gentleman with underlying Stage III B renal cell carcinoma with lung metastasis and gout presented in June 2021 with bilateral red eyes following Coronavirus disease (COVID-19) vaccination.
J Med Chem
January 2025
Epics Therapeutics SA, rue Adrienne Bolland 47, Gosselies 6041, Belgium.
METTL3 is the RNA methyltransferase predominantly responsible for the addition of N-methyladenosine (mA), the most abundant modification to mRNA. The prevalence of mA and the activity and expression of METTL3 have been linked to the appearance and progression of acute myeloid leukemia (AML), thereby making METTL3 an attractive target for cancer therapeutics. We report herein the discovery and optimization of small-molecule inhibitors of METTL3, culminating in the selection of as an proof-of-concept compound.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Department of Urology/State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
Sonodynamic therapy, a treatment modality recently widely used, is capable of disrupting the tumor microenvironment by inducing immunogenic cell death (ICD) and enhancing antitumor immunity during immunotherapy. Erdafitinib, an inhibitor of the fibroblast growth factor receptor, has demonstrated potential benefits for treating bladder cancer. However, Erdafitinib shows effectiveness in only a small number of patients, and the majority of patients responding positively to the medication have "immune-cold" tumors.
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