Joseph J. Cullen's research while affiliated with University of Iowa and other places
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Publications (33)
At pharmacological levels, ascorbate (P-AscH-) acts as a pro-oxidant by generating H2O2, depleting ATP in sensitive cells leading to cell death. The aim of this study was to determine the role of ATP production by oxidative phosphorylation or glycolysis in mechanisms of resistance to P-AscH–induced cell death. Pancreatic cancer cells were used to g...
Internal hernias are relatively rare and are the cause of 0.6% to 5.8% of small bowel obstructions. Incidence of acquired internal hernias is rising secondary to increased use of laparoscopic Roux-en-Y gastric bypass for weight loss and management of obesity-related morbidities. Knowledge of congenital forms of internal hernia is important in recog...
Pharmacological doses (> 1mM) of ascorbate (a.k.a., vitamin C) have been shown to selectively kill cancer cells through a mechanism that is dependent on the generation of H2O2 at doses that are safely achievable in humans using intravenous administration. The process by which ascorbate oxidizes to form H2O2 is thought to be mediated catalytically b...
Recent evidence suggests a significant role of fibroblasts in pancreatic ductal adenocarcinoma (PDAC) stromal cellularity, metabolism, and therapy response. Considering PDAC being an age-associated disease and a dismal 5-y survival of less than 6%, this study investigates whether stromal aging regulates PDAC progression. Results showed that normal...
P-AscH– radiosensitizes pancreatic cancer (PDAC) in vitro and in vivo. The purpose of this Phase I trial is to determine the safety and tolerability of P-AscH- when combined with gemcitabine and radiation. Patients with locally advanced PDAC who were to undergo gemcitabine and radiotherapy were enrolled (Clinical Trials.gov NCT0152890). Patients we...
The toxicity of pharmacological ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Since pancreatic cancer cells are sensitive to H2O2 generated by ascorbate they would also be expected to become sensitized to agents that increase oxidative damage such as ionizing radiation. The current study demonstrates that pharmacol...
Pharmacological ascorbate has been shown to induce toxicity in a wide range of cancer cell lines; using animal models pharmacological ascorbate has shown promise for use in cancer treatment. At pharmacological concentrations the oxidation of ascorbate produces a high flux of H2O2via the formation of ascorbate radical (Asc(•-)). The rate of oxidatio...
Pharmacological ascorbate (AscH(-)) selectively induces cytotoxicity in pancreatic cancer cells vs. normal cells via the generation of extracellular hydrogen peroxide (H2O2), producing double-stranded DNA breaks and ultimately cell death. Catalytic manganoporphyrins (MnPs) can enhance ascorbate-induced cytotoxicity by increasing the rate of AscH(-)...
Importance
Surgical site infections (SSIs) are potentially preventable complications that are associated with excess morbidity and mortality.Objective
To determine the excess costs associated with total, deep, and superficial SSIs among all operations and for high-volume surgical specialties.Design, Setting, and Participants
Surgical patients fr...
Multiple surgical diseases involve the small intestine or appendix and require knowledge relating to operations on the small bowel. This chapter introduces the concepts necessary to operate on the small bowel and appendix safely by discussing the operations in the context of common pathologic entities.
Research in autophagy continues to accelerate,(1) and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.(2,3) There are many useful an...
In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring au...
Fiberoptic endoscopy and colonoscopy have been increasingly employed and expanded for the diagnosis and treatment of various gastrointestinal diseases. Accurate documentation allows the surgeon to review and communicate significant visual observations, endoscopic techniques, and findings. This chapter focuses on the pre-procedure, procedural, and p...
Laparoscopic cholecystectomy has become the operation of choice for gallbladder disease, and the incidence of complications is low. Major complications occurring during surgery or in the immediate postoperative period include hemorrhage, common bile duct injury, bile leak, iatrogenic gallbladder perforation, bowel injury, and retained bile duct sto...
Sedation is an integral part of upper and lower endoscopy and serves to alleviate patient discomfort, reduce risk of injury to the patient, and facilitate optimal examination during the procedure. The majority of patients undergoing endoscopy have sedation provided by the endoscopist. An understanding of commonly used medications and an awareness o...
Pancreatic cancer is the fourth most common cause of cancer death in the USA with greater than 33,000 fatal cases annually in the USA alone, and an overall 5-year survival rate of less than 5%. The relationship between reactive oxygen species (ROS), antioxidants, and possible treatments for pancreatic cancer is discussed in this review. ROS are gen...
Vertical banded gastroplasty (VBG) was initiated in 1980 as a weight loss operation that restricted oral intake.
The aim of our study was to determine the results of patients who presented with complications of the VBG and wanted reversal of the VBG, not a conversion to another gastric weight loss operation.
From 1993 to 2008, 27 patients had rever...
Citations
... The patient-derived cell line (PDX339) was obtained from the Medical College of Wisconsin surgical oncology tissue bank [27]. In addition, MIA PaCa-2 cells were transfected with plasmids containing mUNG1 (pMA3790, RRID: Addgen_70110) or HSV-1 UL12.5M185 (pMA4008, RRID: Addg-ene_70109) gene to generate cells without functional mitochondria (ρ 0 cells) [28]. Mitochondrial expression of DNA repair enzymes mutant Y147A human uracil-N-glycosylase (mUNG1) or Herpes Simplex Virus 1 (HSV-1) protein UL12.5M185 leads to mtDNA depletion and the formation of ρ 0 cells. ...
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... Approximately 30% of cases remain asymptomatic throughout life. [1] ...
... The gastrointestinal stromal tumours (GIST) represents 1% of all gastrointestinal malignancies. [1][2][3][4][5] GIST of the anal canal is extremely rare and there is no widely accepted treatment approach for this neoplasia. Although surgical resection remains the mainstay of treatment, it is still uncertain whether local or radical excision should be appropriate for anal canal GIST. ...
... Feng et al. found Codonopsis pilosula polysaccharide-iron (III) complex could effectively inhibit the growth of A2780 ovarian cancer cells (Feng and Zhang 2020). Besides, a study on sucrose-iron (III) complex proved that iron sucrose could increase intracellular labile iron pools, consequently increasing the toxicity of pharmacological ascorbate in human colon cancer cells by increasing the generation of H 2 O 2 (Brandt et al. 2018). ...
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... Recently, a novel mechanism was suggested; L-ascorbate may target the GAPDH enzyme with oxidation, thus killing only KRASand BRAF-mutant colorectal cancer cells [247]. A recent report is promising for pancreatic cancer [248]. ...
... 20 When endoclips are used, it has been recommended, when transecting the cystic duct, to leave 2.5 mm distal to the most distal endoclip placed on the cystic duct to prevent displacement of the endoclip. 21 In this study, the length of the stump of the cystic duct distal to the endoclip left on the cystic duct was 2.5 mm in both groups. Suture ligation of the cystic duct can also be performed. ...
... Our in vitro, in vivo [12][13][14], and human studies [11], combined with those of others [15], provide a solid foundation for using P-AscH − as a radiosensitizer in PDAC therapy. P-AscH − has been shown to enhance the cytotoxic effects of chemotherapies [16] and radiation in all the PDAC cell lines examined but not in non-tumorigenic pancreatic ductal epithelial cells [17,18]. In mice with established PDAC xenografts, P-AscH − combined with radiation decreased tumor growth and increased survival [18]. ...
... This reasoning is the same as the one behind the use of other H 2 O 2 -producing strategies: radio-and chemotherapy. Oxidation of ascorbate at the expense of endogenous metalloproteins has already been employed in clinical trials in patients with pancreatic cancer [61,62]. The use of Mn porphyrin, MnTE-2-PyP 5 þ and analogs of similar redox properties (MnTnHex-2-PyP 5 þ , MnTnBuOE-2-PyP 5 þ ), optimized for ascorbate oxidation, has been reported by us [3,6,41,43,44] and subsequently by others to bear therapeutic potential [40,42,63]. ...
... It has also been found to be of great use in cell culture due to its stability in aqueous environments. The accumulation of ascorbate in cells when l-ascorbic acid 2-phosphate is provided in the culture medium is somewhat slower than when ascorbate is the source [55], but confounding oxidation in the medium is avoided [56]. ...
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... Our in vitro, in vivo [12][13][14], and human studies [11], combined with those of others [15], provide a solid foundation for using P-AscH − as a radiosensitizer in PDAC therapy. P-AscH − has been shown to enhance the cytotoxic effects of chemotherapies [16] and radiation in all the PDAC cell lines examined but not in non-tumorigenic pancreatic ductal epithelial cells [17,18]. ...
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