MI-63 / Ascenta, Sanofi - LARVOL DELTA

Repeat SABR likely required for survival benefit in oligometastatic colorectal cancer: results from the prospective randomised SABR-SCAN trial (ESTRO 2025) - P=N/A | "Median follow-up for surviving patients was 80 months (min63- max85)... Despite low numbers, SABR seems to reverse progression of oligometastatic CRC without systemic therapy and entail long-term survival, but repeat MDT of all new oligometastatic lesions seems to be required. pPFS significantly correlated with OS and may be a preferable surrogate endpoint for OS compared with PFS when studying the contribution of MDT to survival in LOM."

Clinical • Metastases • Colorectal Cancer • Oncology • Solid Tumor

Increase on environmental seasonality through the European Early Pleistocene inferred from dental enamel hypoplasia. (PubMed, Sci Rep) - "0.86 Ma (i.e., MIS63 and MIS21, respectively). Statistical comparisons show an increase in the frequency of dental hypoplasia between these two chronological periods, thus reinforcing the idea of increased seasonality in the circum-Mediterranean environments during the Early Pleistocene."

Journal

Genome-wide identification of microRNAs involved in the somatic embryogenesis of Eucalyptus. (PubMed, G3 (Bethesda)) - "The genes encoding PIL1 and RPS21C, regulated by up-regulated miRNAs (e.g., egd-N-miR63-5p, egd-N-miR63-5p and MIR169,) were down-regulated exclusively in the dedifferentiation of E. camaldulensis. This is the first time to study the miRNA regulation in the dedifferentiation process of Eucalyptus and it will provide a valuable resource for future studies. More importantly, it will improve our understanding of miRNA regulation during the somatic embryogenesis of Eucalyptus and benefit the Eucalyptus breeding program."

Journal • MIR96 • MIR99A

Targeting mitochondrial proline dehydrogenase with a suicide inhibitor to exploit synthetic lethal interactions with p53 upregulation and glutaminase inhibition. (PubMed, Mol Cancer Ther) - "Fly and breast tumor (MCF7)-xenografted mouse studies indicate that N-PPG doses sufficient to phenocopy PRODH knockout and induce its decay can be safely and effectively administered in vivo Among breast cancer cell lines and tumor samples, PRODH mRNA expression is subtype dependent and inversely correlated with glutaminase (GLS1) expression; combining inhibitors of PRODH (S-5-oxo and N-PPG) and GLS1 (CB-839) produces additive if not synergistic loss of cancer cell (ZR-75-1, MCF7, DU4475, and BT474) growth and viability. Although PRODH knockdown alone can induce cancer cell apoptosis, the anticancer potential of either reversible or irreversible PRODH inhibitors is strongly enhanced when p53 is simultaneously upregulated by an MDM2 antagonist (MI-63 and nutlin-3). However, maximum anti-cancer synergy is observed in vitro when the PRODH suicide inhibitor N-PPG is combined with both GLS1 inhibition and a p53-upregulating MDM2 antagonist. These findings provide preclinical..."

Journal • Breast Cancer • Oncology • Solid Tumor

Small-molecule MDM2 antagonists attenuate the senescence-associated secretory phenotype (AACR 2018) - "Upon treatment with the MDM2 inhibitors nutlin-3a or MI-63, human cells acquired a senescence-like growth arrest, but the arrest was reversible. Importantly, the inhibitors reduced expression of the signature SASP factors IL-6 and IL-1A by cells made senescent by genotoxic stimuli, and suppressed the ability of senescent fibroblasts to stimulate breast cancer cell aggressiveness. Our findings suggest that MDM2 inhibitors could reduce cancer progression in part by reducing the pro-inflammatory environment created by senescent cells."

Breast Cancer

Autopsy and clinical discrepancies in patients undergoing extracorporeal membrane oxygenation: a case series. (PubMed, Cardiovasc Pathol) - "We found major discrepancies between premortem and postmortem diagnoses in patients who underwent ECMO. Our findings underscore difficulties in clinically diagnosing events on ECMO as well as the need for enhanced surveillance and better diagnostic techniques in ECMO patients. Further prospective studies are necessary to understand effects of ECMO on major organs."

Clinical • Journal