There remains a clear need for effective tumor cell purging in autologous stem cell transplantation (ASCT) where residual malignant cells within the autograft contribute to disease relapse. Here we propose the use of a novel Fas agonist with potent pro-apoptotic activity, termed MegaFasL, as an effective ex-vivo purging agent. MegaFasL selectively kills hematological cancer cells from lymphomas and leukemias and prevents tumor development at concentrations that do not reduce the functional capacity of human hematopoietic stem/progenitor cells both in in vitro and in in vivo transplantation models. These findings highlight the potential use of MegaFasL as an ex-vivo purging agent in ASCT.
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http://dx.doi.org/10.1038/bcj.2011.47 | DOI Listing |
J Biol Chem
January 2025
Institute of Biochemistry and Molecular Biology II, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany. Electronic address:
Recently, we phenocopied Interleukin (IL-)6 signaling using the dimerized single-chain variable fragment (scFv) derived from the respiratory syncytial virus (RSV) IgG1-antibody Palivizumab (PLHFc) to activate a Palivizumab anti-idiotypic nanobody (AIP)-gp130 receptor fusion protein. Palivizumab was unable to activate STAT3 signaling, so we aimed to create a similar ligand capable of triggering this pathway. Here, we created three variants of the ligand called PLH0Fc, PLH4Fc and PLH8Fc by shortening the spacer region connecting PLH and Fc from 23 amino acids in PLHFc to 0 amino acids or expanding it by rigid linkers of 4 or 8 alpha helical loops, respectively.
View Article and Find Full Text PDFJ Hepatol
January 2025
Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, United States of America. Electronic address:
Background & Aims: Lanifibranor is a pan-PPAR agonist that improves glucose/lipid metabolism and reverses steatohepatitis and fibrosis in adults with MASH. We tested its effect on insulin resistance at the level of different target tissues in relationship to change in intrahepatic triglyceride (IHTG) content.
Methods: This phase 2, single center, study randomized (1:1) 38 patients with T2D and MASLD to receive lanifibranor 800 mg or placebo for 24 weeks.
Diabetes Obes Metab
January 2025
Boehringer Ingelheim International GmbH, Biberach, Germany.
Aim: To explore the effects of sex and baseline body mass index (BMI) on the efficacy and safety of survodutide in people with a BMI ≥27 kg/m.
Materials And Methods: Totally 387 people (aged 18-75 years, BMI ≥27 kg/m, without diabetes) were randomized 1:1:1:1:1 to once-weekly subcutaneous survodutide (0.6, 2.
J Agric Food Chem
January 2025
State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi, Jiangsu 214122, China.
This study investigated whether the galactooligosaccharide (GOS)-metabolism-related genes (GOS-cluster) in contribute to alleviating glucose and lipid metabolic disorders in type 2 diabetic mice. Genomic analysis of 69 strains based on the GOS-cluster, combined with in vitro fermentation experiments, revealed that high-GOS-cluster strains (≥24 MFS, ≥39 GOS-cluster) demonstrated superior GOS utilization and bile salt tolerance. In vivo the high-GOS-cluster strains resulted in a significant reduction of blood glucose levels by 18.
View Article and Find Full Text PDFBiomolecules
December 2024
Molecular Oncology Laboratory, Cell Differentiation and Cancer Research Unit, UMIEZ Campus II FES Zaragoza, National Autonomous University of Mexico, Mexico City 09230, Mexico.
Cervical cancer is a global health problem; therapies focused on eliminating tumour cells and strengthening different immunotherapies are in development. However, it has been observed that cervical tumour cells can evade cell death mechanisms and generate immune system molecules to promote their proliferation and metastasis. In this context, we analysed the role of the IL-2 and CD95 pathways, essential molecules in activating the immune system and eliminating tumour cells.
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