ABSTRACT
Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic state substantially enhances the efficacy of conventional single- and multi-agent chemotherapy regimens against PDAC. Molecular analyses of tumors exposed to high glucose levels reveal that the expression of GCLC (glutamate-cysteine ligase catalytic subunit), a key component of glutathione biosynthesis, is diminished, which in turn augments oxidative anti-tumor damage by chemotherapy. Inhibition of GCLC phenocopies the suppressive effect of forced hyperglycemia in mouse models of PDAC, while rescuing this pathway mitigates anti-tumor effects observed with chemotherapy and high glucose.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Animals , Mice , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Administration, Cutaneous , Glucose , Pancreatic NeoplasmsABSTRACT
Ureteroarterial fistula (UAF) is a rare and life-threatening source of hematuria. A high index of suspicion is warranted for early diagnosis and timely intervention. Because of high perioperative risk and comorbidities in UAF patients, the endovascular approach has become preferred for repair. Infection can complicate this mode of therapy, and treatment with antibiotics is important. Herein we present five cases of secondary UAFs treated with stent graft alone or stent graft and embolization.
