Gliomas are the most common primary brain tumours. Several independent studies have shown that isocitrate dehydrogenase 1 (IDH1) mutation in diffuse gliomas is associated with a more favourable patient outcome. The aim of this study was to evaluate the prognostic relevance of an antibody specifically detecting the R132H point mutation of IDH1 in tissue sections in a large series of human gliomas. Surgical specimens of 220 consecutive patients with infiltrative low and high-grade gliomas were included in this retrospective study. In multivariate analysis, IDH expression did not reach significance (p = 0.122) in regard to prognosis, in contrast to WHO grade and age at time of surgery (p < 0.001, Cox regression). A significant correlation of p53 expression to mutated IDH1 and histological grading and an inverse correlation to truncated EGFR expression were observed (p < 0.001, Mann-Whitney test). In sum, our results indicate that IDHR132H mutation correlates significantly with p53 and inversely with EGFR mutations. Further studies should investigate whether these correlations reflect involvement of these three molecules in a common signalling pathway.
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Blood
January 2025
University of Chicago, Chicago, Illinois, United States.
Most diffuse large B-cell lymphoma (DLBCL) patients treated with immunotherapies such as bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was applied to multiple large independent datasets in order to characterize DLBCL immune environments, and to define their association with tumor cell-intrinsic genomic alterations and outcomes to CD19-directed CAR T-cell and CD20 x CD3 BsAb therapies. This approach effectively segregated DLBCLs into four immune quadrants (IQ) defined by cell-of-origin and immune-related gene set expression scores.
View Article and Find Full Text PDFPurpose: Outcomes for patients with advanced sarcomas are poor and there is a high unmet need to develop novel therapies. The purpose of this phase I study was to define the safety and efficacy of botensilimab (BOT), an Fc-enhanced anti-cytotoxic lymphocyte-association protein-4 antibody, plus balstilimab (BAL), an anti-PD-1 antibody, in advanced sarcomas.
Methods: BOT was administered intravenously (IV) at 1 mg/kg or 2 mg/kg once every 6 weeks in combination with BAL IV at 3 mg/kg once every 2 weeks for up to 2 years.
Tree Physiol
January 2025
Institute of Soil and Water Conservation, Northwest A&F University, Yangling 712100, China.
Modulation of stomatal development and movement is a promising approach for creating water-conserving plants. Here, we identified and characterized the PagHCF106 gene of poplar (Populus alba × Populus glandulosa). The PagHCF106 protein localized predominantly to the chloroplast, and the PagHCF106 gene exhibited tissue-specific expression pattern.
View Article and Find Full Text PDFPLoS Genet
January 2025
Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, Brisbane, Australia.
Adaptation to existence outside the womb is a key event in the life of a mammal. The absence of macrophages in rats with a homozygous mutation in the colony-stimulating factor 1 receptor (Csf1r) gene (Csf1rko) severely compromises pre-weaning somatic growth and maturation of organ function. Transfer of wild-type bone marrow cells (BMT) at weaning rescues tissue macrophage populations permitting normal development and long-term survival.
View Article and Find Full Text PDFChem Biodivers
January 2025
Kasetsart University - Bangkhen Campus, Chemistry, 50 Ngamwongwan Road, 10900, Bangkok, THAILAND.
A terpene synthase gene (mtas) from Menisporopsis theobromae BCC 4162 was heterologously expressed in Aspergillus oryzae NSAR1, resulting in the production of (+)-aristolochene. Mutations were introduced in MtAS at aromatic residues (Y83, F103, F169, and W323) surrounding the active site, which are critical for precursor cyclisation and intermediate stabilisation during aristolochene biosynthesis. Transformants harbouring mutated mtas, specifically F103W, F169A and F169W, produced (2R,4S,5R,7S)-2-hydroxyaristolochene as the major product, along with aristolochene and other tentative metabolites, including germacrene A and sesquiterpenoids.
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