Chronic lymphocytic leukaemia (CLL) is a progressive disease, commonly treated in its early stage with alkylating agents. A multi-agent regimen which includes anthracyclines is used to treat advanced disease. Despite chemotherapy, the disease remains incurable. There is now considerable evidence to suggest that anthracyclines exert their effect via the nuclear enzyme topoisomerase II and that alterations in amount or activity of this enzyme may mediate drug resistance. We have investigated topoisomerase II mRNA expression in 34 CLL patients and in haemopoietic cells from 10 normal donors. Expression was found to be low but detectable in all patients and normals. Such low levels may contribute to the toxicity of alkylating agents, but could severely limit the effect of anthracyclines.
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Transplant Cell Ther
January 2025
Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Pediatrics, University of Cincinnati, Cincinnati, OH.
Background: HSCT conditioning regimens cause massive lysis of hematopoietic cells with release of toxic intracellular molecules into the circulation.
Objectives: To describe the response to oxidative stress early after hemopoietic stem cell transplantation (HSCT) and assess the association of early oxidative stress with later transplant outcomes.
Study Design: Key components of in the body's physiological response to oxidative stress were studied in a cohort of 122 consecutive pediatric allogeneic HSCT recipients.
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January 2025
Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
Background: Adaptive cellular therapy (ACT), particularly chimeric antigen receptor (CAR)-T cell therapy, has been successful in the treatment of hemopoietic malignancies. However, poor trafficking of administered effector T cells to the tumor poses a great hurdle for this otherwise powerful therapeutic approach in solid cancers. Our previous study revealed that targeting CD93 normalizes tumor vascular functions to improve immune checkpoint blockade therapy.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, State Key Laboratory of Luminescent Materials and Devices, School of Materials Science and Engineering, AIE Institute, South China University of Technology, Guangzhou, 510640, China.
Photodynamic therapy holds great potentials in cancer treatment, yet its effectiveness in hypoxic solid tumor is limited by the oxygen-dependence and insufficient oxidative potential of conventional type II reactive oxygen species (ROS). Herein, the study reports a supramolecular photosensitizer, BSA@TPE-BT-SCT NPs, through encapsulating aggregation-enhanced emission photosensitizer by bovine serum albumin (BSA) to significantly enhance ROS, particularly less oxygen-dependent type I ROS for photodynamic immunotherapy. The abundant type I ROS generated by BSA@TPE-BT-SCT NPs induce multiple forms of programmed cell death, including apoptosis, pyroptosis, and ferroptosis.
View Article and Find Full Text PDFJ Cell Mol Med
January 2025
Department of Hematology, General Hospital, Tianjin Medical University, Tianjin, China.
Single-cell sequencing of lineage negative (Lin-) cells from patients with myelodysplastic syndromes (MDS) revealed a reduction in ferritin heavy chain 1 (FTH1) levels, yet the significance of this decrease in FTH1 in the pathophysiology of MDS remains unclear. In this study, we evaluated the role of FTH1 in patients with MDS. The mRNA expression of FTH1 in GlycoA nucleated erythrocytes from MDS patients was significantly lower than that in control group.
View Article and Find Full Text PDFInt J Biol Sci
January 2025
Department of Basic & Translational Sciences, School of Dental Medicine, University of Pennsylvania, USA.
Inositol polyphosphate-5-phosphatase E (INPP5E) is a 5-phosphatase critically involved in diverse physiological processes, including embryonic development, neurological function, immune regulation, hemopoietic cell dynamics, and macrophage proliferation, differentiation, and phagocytosis. Mutations in cause Joubert and Meckel-Gruber syndromes in humans; these are characterized by brain malformations, microphthalmia, situs inversus, skeletal abnormalities, and polydactyly. Recent studies have demonstrated the key role of INPP5E in governing intracellular processes like endocytosis, exocytosis, vesicular trafficking, and membrane dynamics.
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