XIAN ZHANG¹, ZHUANG ZHOU², JUNZHE WANG¹, MENGMENG HAN¹, HAN LIU¹, MEIRONG ZANG¹, JIANNING LIU¹, JIAPEI LU¹, JINQIAO ZHANG¹, GUOCHUAN ZHANG^2,*, LIXIA SUN^1,#,*

BIOCELL, Vol.48, No.2, pp. 303-311, 2024, DOI:10.32604/biocell.2023.046640

Abstract Background: Prognosis of multiple myeloma (MM) patients with extramedullary disease (EMD) remains poor. T cell dysfunction and an immunosuppressive environment have been reported in the bone marrow (BM) of MM patients. However, the immunosuppressive microenvironment and immune checkpoint receptors (ICRs) on CD8 T cells in the EMD tissue of newly diagnosed MM (NDMM) patients have not been thoroughly studied. Methods: We investigated the expression levels of T cell immunoglobulin mucin-domain-containing-3 (TIM-3) and T-cell immunoglobulin and ITIM domain (TIGIT) on CD8 T cells and the expression of their ligands (Galectin-9 and CD155) on myeloma cells in EMD tissue of NDMM patients.… More > Graphic Abstract

XINTONG LIU^1,2,3, EMIKO SANADA^1,3,4, JIANG LI⁵, XIAOMENG LI⁶, HIROYUKI OSADA^1,4,7,*, NOBUMOTO WATANABE^1,2,3,*

Oncology Research, Vol.31, No.5, pp. 645-654, 2023, DOI:10.32604/or.2023.030240

Abstract β-transducin repeat-containing protein (β-TrCP) is an F-box protein subunit of the E3 Skp1-Cullin-F box (SCF) type ubiquitin-ligase complex, and provides the substrate specificity for the ligase. To find potent ligands of β-TrCP useful for the proteolysis targeting chimera (PROTAC) system using β-TrCP in the future, we developed a high-throughput screening system for small molecule β-TrCP ligands. We screened the chemical library utilizing the system and obtained several hit compounds. The effects of the hit compounds on in vitro ubiquitination activity of SCF^β-TrCP1 and on downstream signaling pathways were examined. Hit compounds NPD5943, NPL62020-01, and NPL42040-01 inhibited the TNFα-induced degradation of… More > Graphic Abstract