ABSTRACT
Small cell lung cancer (SCLC) is one of the deadliest human cancers, with a 5-year survival rate of â¼7%. Here, we performed a targeted proteomics analysis of human SCLC samples and thereby identified hypoxanthine phosphoribosyltransferase 1 (HPRT1) in the salvage purine synthesis pathway as a factor that contributes to SCLC malignancy by promoting cell survival in a glutamine-starved environment. Inhibition of HPRT1 by 6-mercaptopurine (6-MP) in combination with methotrexate (MTX), which blocks the de novo purine synthesis pathway, attenuated the growth of SCLC in mouse xenograft models. Moreover, modulation of host glutamine anabolism with the glutamine synthetase inhibitor methionine sulfoximine (MSO) in combination with 6-MP and MTX treatment resulted in marked tumor suppression and prolongation of host survival. Our results thus suggest that modulation of host glutamine anabolism combined with simultaneous inhibition of the de novo and salvage purine synthesis pathways may be of therapeutic benefit for SCLC.
ABSTRACT
Acute fatty liver of pregnancy (AFLP) is a rare disorder that typically develops in the third trimester. We successfully diagnosed and treated a case of AFLP that developed at 18 weeks' gestation. A 34-year-old woman-gravida 4, para 3-presented with continuous vomiting and abdominal pain and developed convulsive seizures and lost consciousness after transfusion therapy. Cerebral apoplexy was excluded by computed tomography of the brain. Blood tests revealed severe metabolic acidosis, coagulopathy, and leukocytosis, followed by severe hypoglycemia and elevated levels of transaminases and ammonia. The fetus was delivered dead. Whole-body computed tomography showed fatty liver. The patient was diagnosed with AFLP based on the Swansea criteria. AFLP may be a differential diagnosis in the second trimester, and rapid termination should be considered as radical treatment. Starvation may be a risk factor for this disorder.
