The effects of proteosome inhibitor Bortezomib (BZ) were studied in vitro for 24 h on the protein kinase C (PKC) profiles, rates of proliferation and apoptosis in Jurkat cells and lymphocytes of 10 patients with systemic lupus erythematosus (SLE) and nine healthy subjects. The expressions of PKC proteins, the rates of proliferation and apoptosis were determined. The effects of BZ were different in the Jurkat and lupus T cells. Whereas BZ elevated the expression of PKC θ, δ and ξ isoenzymes in the Jurkat cells, it was unable to do that in the lupus T cells. BZ induced a dose-dependent increase in the apoptosis of Jurkat cells, while decreased the proliferation. The same effect of BZ was observed on the apoptosis of lymphocytes both in SLE and healthy subjects at concentrations higher than the therapeutic dose. We conclude that BZ treatment in vitro was not able to restore the SLE-specific defect (decrease) in the expression of PKC isoenzymes in the T cells as it was expected. This can be a limiting factor in the positive clinical effects of BZ in lupus.
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http://dx.doi.org/10.1111/j.1365-3083.2011.02647.x | DOI Listing |
Bioorg Med Chem
January 2025
Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, #555 Zu Chong Zhi Road, Shanghai 201203 China; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Qixia District, Nanjing 210023 China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024 China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:
Hematopoietic progenitor kinase 1 (HPK1) has emerged as a promising target for cancer immunotherapy due to its critical role as a negative regulator of T cell receptor (TCR) signaling. Despite this potential, no HPK1 inhibitors have been approved for cancer treatment, underscoring the need for structurally novel inhibitors. Herein, we describe the design, synthesis and biological evaluation of a series of potent HPK1 inhibitors based on our previously identified hit 9.
View Article and Find Full Text PDFAsian Pac J Cancer Prev
January 2025
Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Background: Acute Lymphoblastic Leukemia (ALL) is the most common type of leukemia among children. There are several types of drugs that are common in treating and controlling leukemia, including 6-M. Moreover, the anti-cancer effects of the Thiosemicarbazone-Ni complex were surveyed as well as 6-MP.
View Article and Find Full Text PDFJ Inflamm Res
January 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
Purpose: Oral lichen planus (OLP) is a chronic, immune-mediated inflammatory disease involving T cells. Mitochondrial fission plays a crucial role in T cell fate through structural remodeling. Nicotinamide adenine dinucleotide (NAD) regulates mitochondrial remodeling and function.
View Article and Find Full Text PDFBMC Biol
January 2025
School of Life Sciences, Zhengzhou University, Zhengzhou, 450001, China.
Background: Poliovirus receptor (PVR) and its receptor system, including TIGIT, CD226, and CD96, play a pivotal role in orchestrating tumor immune evasion. Upon engagement with PVR on tumor cells, CD96 exerts inhibitory effects on the function of T cells and NK cells, thereby fostering tumor immune evasion. Therefore, screening of immune checkpoint inhibitors (ICIs) targeting the CD96/PVR pathway will provide promising candidates for tumor immunotherapy.
View Article and Find Full Text PDFVirology
January 2025
The Wistar Institute of Anatomy and Biology, Philadelphia, PA, USA. Electronic address:
J-Lat cells are derivatives of the Jurkat CD4 T cell line that contain a non-infectious, inducible HIV provirus with a GFP tag. While these cells have substantially advanced our understanding of HIV latency, their use by many laboratories in low and middle-income countries is restricted by limited access to flow cytometry. To overcome this barrier, we describe a modified J-Lat assay using a standard microplate reader that detects HIV-GFP expression following treatment with latency-reversing agents (LRAs).
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