Pharmacologic Ascorbate Radiosensitizes Pancreatic Cancer but Radioprotects Normal Tissue: The Role of Oxidative Stress-Induced Lipid Peroxidation.

The toxicity of ionizing radiation limits its effectiveness in the treatment of pancreatic ductal adenocarcinoma. Pharmacologic ascorbate (P-AscH) has been shown to radiosensitize pancreatic cancer cells while simultaneously radioprotecting normal cells. We hypothesize that P-AscH protects the small intestine while radiosensitizing pancreatic cancer cells partially through an oxidative stress mechanism.

Pharmacologic Ascorbate and DNMT Inhibitors Increase DUOX Expression and Peroxide-Mediated Toxicity in Pancreatic Cancer.

Recent studies have demonstrated an important role for vitamin C in the epigenetic regulation of cancer-related genes via DNA demethylation by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. DNA methyltransferase (DNMT) reverses this, increasing DNA methylation and decreasing gene expression. Dual oxidase (DUOX) enzymes produce hydrogen peroxide (HO) in normal pancreatic tissue but are silenced in pancreatic cancer (PDAC).

Pharmacological ascorbate induces sustained mitochondrial dysfunction.

Pharmacological ascorbate (P-AscH; high dose given intravenously) generates HO that is selectively cytotoxic to cancer compared to normal cells. The RAS-RAF-ERK1/2 is a major signaling pathway in cancers carrying RAS mutations and is known to be activated by HO. Activated ERK1/2 also phosphorylates the GTPase dynamin-related protein (Drp1), which then stimulates mitochondrial fission.

Pharmacological Ascorbate Enhances Chemotherapies in Pancreatic Ductal Adenocarcinoma.

Objectives: Pharmacological ascorbate (P-AscH - , high-dose, intravenous vitamin C) has shown promise as an adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) treatment. The objective of this study was to determine the effects of P-AscH - when combined with PDAC chemotherapies.

Methods: Clonogenic survival, combination indices, and DNA damage were determined in human PDAC cell lines treated with P-AscH - in combination with 5-fluorouracil, paclitaxel, or FOLFIRINOX (combination of leucovorin, 5-fluorouracil, irinotecan, oxaliplatin).

Auranofin and Pharmacologic Ascorbate as Radiomodulators in the Treatment of Pancreatic Cancer.

Pancreatic cancer accounts for nearly one fourth of all new cancers worldwide. Little progress in the development of novel or adjuvant therapies has been made over the past few decades and new approaches to the treatment of pancreatic cancer are desperately needed. Pharmacologic ascorbate (P-AscH, high-dose, intravenous vitamin C) is being investigated in clinical trials as an adjunct to standard-of-care chemoradiation treatments.

Robotic surgery training during general surgery residency: a survey comparing attitudes towards a robotic training curriculum within general surgery, urology, and OBGYN residents and attendings.

General surgery residents are increasingly exposed to robotic surgery during their training. However, there is no standardized robotic educational curriculum across United States residency programs. Prior to implementing a robotic surgery curriculum, we surveyed our residents and attendings to ascertain their attitude towards robotic surgery training in residency.

Impact of EcSOD Perturbations in Cancer Progression.

Reactive oxygen species (ROS) are a normal byproduct of cellular metabolism and are required components in cell signaling and immune responses. However, an imbalance of ROS can lead to oxidative stress in various pathological states. Increases in oxidative stress are one of the hallmarks in cancer cells, which display an altered metabolism when compared to corresponding normal cells.

Catalase Modulates the Radio-Sensitization of Pancreatic Cancer Cells by Pharmacological Ascorbate.

Pancreatic cancer cells (PDACs) are more susceptible to an oxidative insult than normal cells, resulting in greater cytotoxicity upon exposure to agents that increase pro-oxidant levels. Pharmacological ascorbate (P-AscH), i.e.