Cinchonine exerts anti-tumor and immunotherapy sensitizing effects in lung cancer by impairing autophagic-lysosomal degradation.

Currently, there are several treatments approaches available for lung cancer; however, patients who develop drug resistance or have poor survival rates urgently require new therapeutic strategies for lung cancer. In autophagy, damaged proteins or organelles are enclosed within autophagic vesicles with a bilayer membrane structure and transported to the lysosomes for degradation and recirculation. Autophagy is a crucial pathway involved in the clearance of reactive oxygen species (ROS) and damaged mitochondria. Meanwhile, inhibiting autophagy is a promising strategy for cancer treatment. In this study, we found for the first time that Cinchonine (Cin) can act as an autophagy suppressor and exert anti-tumor effects. Cin significantly inhibited the proliferation, migration, and invasion of cancer cells in vitro and the tumor growth and metastasis in vivo, without obvious toxic effects. We found that Cin suppressed the autophagic process by blocking autophagosome degradation through the inhibition of the maturation of lysosomal hydrolases. Cin-mediated autophagy inhibition resulted in the elevated ROS level and the accumulation of damaged mitochondria, which in turn promoted apoptosis. N-acetylcysteine, a potential ROS scavenger, significantly suppressed Cin-induced apoptosis. Additionally, Cin upregulated programmed death-ligand 1 (PD-L1) expression in lung cancer cells by inhibiting autophagy. Compared with monotherapy and control group, the combined administration of anti-PD-L1 antibody and Cin significantly reduced tumor growth. These results suggest that Cin exerts anti-tumor effects by inhibiting autophagy, and that the combination of Cin and PD-L1 blockade has synergistic anti-tumor effects. The data demonstrates the significant clinical potential of Cin in lung cancer treatment.

Plasma exchange improves outcome of sepsis-associated liver failure: A case report.

RATIONALE: Sepsis-associated liver failure is characterized by increased bilirubin levels and coagulation disorders, which has a significant impact on mortality due to the insufficient understanding of its complicated pathogenesis pathophysiology and a lack of standardized treatment. PATIENT CONCERNS: A 56-year-old woman presented signs of sepsis on the 2nd day after undergoing ureteroscopy for left ureter and laparoscopy for lysis of adhesions around left ureter due to hydronephrosis. Her condition seemed to have been improved after treatment, but the bilirubin levels suddenly increased drastically with presence of coagulation disorders. DIAGNOSIS: Laboratory tests combined with her medical history confirmed the diagnosis as sepsis-associated liver failure. INTERVENTIONS: Plasma exchange was applied after hepatoprotective drugs, and other supportive therapies were given which did not significantly improve the condition. OUTCOMES: Laboratory liver function tests indicated the restoration of damaged liver function after plasma exchange was performed and the patient was soon transferred from intensive care unit back to the general ward. LESSONS: Plasma exchange might be a vital and effective therapy to improve outcome of sepsis associated liver failure especially when conventional support therapy is ineffective.