P8-D6 is a novel dual inhibitor of human topoisomerase I (TOP1) and II (TOP2) with broad pro-apoptotic antitumor activity. NCI-60 screening revealed markedly improved cytotoxicity of P8-D6 against solid and leukemia cell lines compared with other single and dual topoisomerase inhibitors, for example, irinotecan, doxorubicin, or pyrazoloacridine. In this study, we investigated the capacity of P8-D6 to inhibit myeloma cell growth and Growth inhibition assays demonstrated significant anti-myeloma effects against different myeloma cell lines with IC values in the low nanomolar range. Freshly isolated plasma cells of patients with multiple myeloma were killed by P8-D6 with similar doses. P8-D6 activated caspase 3/7 and induced significant apoptosis of myeloma cells. Supportive effects of bone marrow stromal cells on IL6-dependent INA-6 myeloma cells were abrogated by P8-D6 and apoptosis occurred in a time- and dose-dependent manner. Of note, healthy donor peripheral blood mononuclear cells and human umbilical vein endothelial cells were not affected at concentrations toxic for malignant plasma cells. Treatment of myeloma xenografts in immunodeficient SCID/beige mice by intravenous and, notably, also oral application of P8-D6 markedly inhibited tumor growths, and significantly prolonged survival of tumor-bearing mice.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1158/1535-7163.MCT-21-0119 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Pilot Study of the Gut Microbiota in Spine Fusion Surgery Patients.
HSS J
February 2025
Hospital for Special Surgery, New York, NY, USA.
Background: The microbiome has been identified as a contributor to bone quality. As skeletal health is critical to success of orthopedic surgery, the gut microbiome may be a modifiable factor associated with postoperative outcomes. For spine fusion surgery in particular, bone formation and sufficient bone mineral density are essential for successful outcomes.
View Article and Find Full Text PDFMicro-Electro Nanofibrous Dressings Based on PVDF-AgNPs as Wound Healing Materials to Promote Healing in Active Areas.
Int J Nanomedicine
January 2025
Department of Burns and Plastic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
Purpose: The purpose of this study is to develop an innovative solution for chronic wounds in high-mobility areas, such as joints, where conventional treatments are hindered by passive healing mechanisms and the need for immobilization. By designing a micro-electro-Nanofiber dressing composed of piezoelectric polyvinylidene fluoride (PVDF) integrated with antimicrobial silver nanoparticles (AgNPs), this research aims to address the dual challenges of promoting effective wound healing and maintaining joint mobility.
Methods: Herein, we developed a novel micro-electro-Nanofiber dressing using electrospinning technology, incorporating polyvinylidene fluoride (PVDF) with silver nanoparticles (AgNPs).
3D bio-printed proteinaceous bioactive scaffold loaded with dual growth factor enhanced chondrogenesis and in situ cartilage regeneration.
Bioact Mater
April 2025
Department of Regenerative Medicine, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
Articular cartilage has a limited self-healing capacity, leading to joint degeneration and osteoarthritis over time. Therefore, bioactive scaffolds are gaining attention as a promising approach to regenerating and repairing damaged articular cartilage through tissue engineering. In this study, we reported on a novel 3D bio-printed proteinaceous bioactive scaffolds combined with natural porcine cancellous bone dECM, tempo-oxidized cellulose nanofiber (TOCN), and alginate carriers for TGF-β1, FGF-18, and ADSCs to repair cartilage defects.
View Article and Find Full Text PDFinhibits -induced inflammatory response through targeting HMGB1 in mouse primary peritoneal macrophages.
Heliyon
January 2025
Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Background: () is one of the most common pathogens associated with deep fungal infection, which represents a serious threat to human health. Although high mobility group box 1 (HMGB1) plays a key role in infection, its mechanism is unclear. We aimed to explore the regulation of small-molecule non-coding RNA (miRNA) for HMGB1 in infection.
View Article and Find Full Text PDFBroad-Temperature Optical Thermometry via Dual Sensitivity of Self-Trapped Excitons Lifetime and Higher-Order Phonon Anharmonicity in Lead-Free Perovskites.
Angew Chem Int Ed Engl
January 2025
DICP: Chinese Academy of Sciences Dalian Institute of Chemical Physics, State Key Laboratory of Molecular Reaction Dynamics and Dalian Coherent Light Source, CHINA.
Broad-temperature optical thermometry necessitates materials with exceptional sensitivity and stability across varied thermal conditions, presenting challenges for conventional systems. Here, we report a lead-free, vacancy-ordered perovskite Cs2TeCl6, that achieves precise temperature sensing through a novel combination of self-trapped excitons (STEs) photoluminescence (PL) lifetime modulation and unprecedented fifth-order phonon anharmonicity. The STEs PL lifetime demonstrates a highly temperature-sensitive response from 200 to 300 K, ideal for low-to-intermediate thermal sensing.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!