SULT1A1-dependent sulfonation of alkylators is a lineage-dependent vulnerability of liver cancers.

Adult liver malignancies, including intrahepatic cholangiocarcinoma and hepatocellular carcinoma, are the second leading cause of cancer-related deaths worldwide. Most individuals are treated with either combination chemotherapy or immunotherapy, respectively, without specific biomarkers for selection. Here using high-throughput screens, proteomics and in vitro resistance models, we identify the small molecule YC-1 as selectively active against a defined subset of cell lines derived from both liver cancer types. We demonstrate that selectivity is determined by expression of the liver-resident cytosolic sulfotransferase enzyme SULT1A1, which sulfonates YC-1. Sulfonation stimulates covalent binding of YC-1 to lysine residues in protein targets, enriching for RNA-binding factors. Computational analysis defined a wider group of structurally related SULT1A1-activated small molecules with distinct target profiles, which together constitute an untapped small-molecule class. These studies provide a foundation for preclinical development of these agents and point to the broader potential of exploiting SULT1A1 activity for selective targeting strategies.

Missed diagnosis of femoral deep artery rupture after femoral shaft fracture: A case report.

BACKGROUND: Vascular injury is a rare complication of femoral shaft fractures, and rupture of the deep femoral artery is more difficult to diagnose because of its anatomical location and symptoms. Despite its low incidence, deep femoral artery rupture can lead to life-threatening outcomes, such as compartment syndrome, making early identification and diagnosis critical. CASE SUMMARY: A 45-year-old male patient was admitted to our hospital due to right lower limb trauma in a car accident, with complaints of severe pain and swelling on his right thigh. X-ray demonstrated a right femoral shaft fracture. During preparation for emergency surgery, his blood pressure and blood oxygen saturation dropped, and sensorimotor function was lost. Computed tomography angiography was performed immediately to confirm the diagnosis of rupture of the deep femoral artery and compartment syndrome, so fasciotomy and vacuum-assisted closure were performed. Rhabdomyolysis took place after the operation and the patient was treated with appropriate electrolyte correction and diuretic therapy. Twenty days after the fasciotomy, treatment with the Hoffman Type II External Fixation System was planned, but it was unable to be immobilized internally based on a new esophageal cancer diagnosis. We kept the external fixation for 1 year, and 3 years of follow-up showed improvement of the patient's overall conditions and muscle strength. CONCLUSION: For patients with thigh swelling, pain, anemia, and unstable vital signs, anterior femoral artery injury should be highly suspected. Once diagnosed, surgical treatment should be performed immediately and complications of artery rupture must be suspected and addressed in time.