PAX3-FOXO1 drives targetable cell state-dependent metabolic vulnerabilities in rhabdomyosarcoma.

PAX3-FOXO1, an oncogenic transcription factor, drives a particularly aggressive subtype of rhabdomyosarcoma (RMS) by enforcing gene expression programs that support malignant cell states. Here we show that PAX3-FOXO1 RMS cells exhibit altered pyrimidine metabolism and increased dependence on enzymes involved in pyrimidine synthesis, including dihydrofolate reductase (DHFR). Consequently, PAX3-FOXO1 cells display increased sensitivity to inhibition of DHFR by the chemotherapeutic drug methotrexate, and this dependence is rescued by provision of pyrimidine nucleotides.

SABR tolerance after prostatectomy: pushing the boundaries of ultrahypofractionation.

Objective: To evaluate the feasibility and tolerance of ultra-hypofractionated SABR (stereotactic ablative radiation therapy) protocol following radical prostatectomy.

Patients And Methods: We included patients undergoing adjuvant or salvage SABR between April 2019 and April 2023 targeting the surgical bed and pelvic lymph nodes up to a total dose of 36.25 Gy (7.

Discontinuous Structural Transitions in Fluids with Competing Interactions.

This paper explores how competing interactions in the intermolecular potential of fluids affect their structural transitions. This study employs a versatile potential model with a hard core followed by two constant steps, representing wells or shoulders, analyzed in both one-dimensional (1D) and three-dimensional (3D) systems. Comparing these dimensionalities highlights the effect of confinement on structural transitions.

P300/RNA polymerase II mediates induction of the teleost viral RNA sensor MDA5 through the interferon regulatory factor IRF11.

Melanoma differentiation-associated gene 5 (MDA5) initiates type I interferon (IFN) production by detecting cytosolic viral RNA. Mammalian MDA5 is an IFN-inducible gene and controlled by IFN regulatory factor 1 (IRF1). Teleost MDA5 also induces type I IFN production in response to viruses, yet its regulation remains largely unexplored.

Biomarker-Directed Radiotherapy in Breast Cancer: A Narrative Review.

Importance: Integration of molecular biomarker information into systemic therapy has become standard practice in breast cancer care. However, its implementation in guiding radiotherapy (RT) is slower. Although postoperative RT is recommended for most patients after breast-conserving surgery and, depending on risk factors, following mastectomy, emerging evidence has indicated that patients with low scores on gene expression signatures or selected clinical-pathological features may have very low local recurrence rates.