Antioxidant Status and Oxidative Stress Markers in Pancreatic Cancer and Chronic Pancreatitis

Kodydková, Jana; Vávřová, Lucie; Staňková, Barbora; Macášek, Jaroslav; Krechler, T; A, Žák

doi:10.1097/mpa.0b013e318288360a

Cited by 74 publications

(57 citation statements)

References 41 publications

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“…Approximately 95% of all PDA show acquisition of a Kras mutation (Hruban et al, 2001) and many of these tumors also have increased cellular oxidative stress levels (Kodydkova et al, 2013), as confirmed by staining for protein adducts formed from ROS-generated reactive lipids such as 4-hydroxy-2-nonenal (4HNE) (Fig. 1A).…”

Section: Resultsmentioning

confidence: 91%

“…The resulting presence of high levels of hydrogen peroxide correlated with an increase in oxidized low density lipoproteins (LDL) (Kodydkova et al, 2013). Analyses of tissue samples from p48 cre ;LSL-Kras G12D mice indicate that ROS already are induced in acinar cells and gradually-increased during ADM and PanIN formation and progression (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions

et al. 2016

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SUMMARY The development of pancreatic cancer requires the acquisition of oncogenic Kras mutations and up-regulation of growth factor signaling, but the relationship between these is not well established. We here show that mutant Kras alters mitochondrial metabolism in pancreatic acinar cells, resulting in increased generation of mitochondrial reactive oxygen species (mROS). Mitochondrial ROS then drives the dedifferentiation of acinar cells to a duct-like progenitor phenotype and progression to PanIN. This is mediated via the ROS-receptive kinase Protein Kinase D1 and the transcription factors NF-κB1 and NF-κB2, which up-regulate expression of the epidermal growth factor, its ligands and their sheddase ADAM17. In vivo, intercepting Kras-mediated generation of mROS reduced the formation of pre-neoplastic lesions. Hence, our data provide insight into how oncogenic Kras interacts with growth factor signaling to induce the formation of pancreatic cancer.

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Section: Resultsmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions

et al. 2016

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“…Reactive oxygen species (ROS) have high impact on physiological and pathological status by inducing oxidative stress mediated inflammatory response in several tissues [5]. Increased status of ROS is also an important factor to develop colitis associated colon cancer [6] and it becomes into oxyradical overload disorder [7]. Oxidative stress in colonic mucosa was counter balanced through endogenous anti-oxidant defense portal systems including superoxide dismutase, catalase and glutathione peroxidase myeloperoxidase to decompose ROS which generate in response to inflammatory stimuli [8].…”

Section: Introductionmentioning

confidence: 99%

Carvacrol exhibits anti-oxidant and anti-inflammatory effects against 1, 2-dimethyl hydrazine plus dextran sodium sulfate induced inflammation associated carcinogenicity in the colon of Fischer 344 rats

Arigesavan

Sudhandiran

2015

Biochemical and Biophysical Research Communications

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“…TAC has been reported to be decreased in cancer patients (32); TAC is thus considered to be a significant marker for diagnosing cancers of the lung (33), breast (34,35), stomach (36), colon (37), and Barrett's esophagus (38). Although reduced antioxidant capacity has been noted in pancreatic cancer, this has not been observed in ampullary cancer, IPMN, or CCA (39).…”

Section: Introductionmentioning

confidence: 97%

Roles of serum and biliary CEA, CA19-9, VEGFR3, and TAC in differentiating between malignant and benign biliary obstructions

İnce

Yıldız²,

Baysal³

et al. 2014

Turk J Gastroenterol

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Background/Aims: Despite the presence of many diagnostic methods, the differential diagnosis between benign and malignant biliary obstructions is still not easy. We aimed to evaluate the role of serum/biliary carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), vascular endothelial growth factor receptor-3(VEGFR-3), and total antioxidant capacity (TAC) tests in this differential diagnosis. Materials and Methods: Patients (n:225; 110♂, 115♀) with diagnosis of malignant (n:96) or benign (n:129) biliary obstruction were included in this cross-sectional study. Serum and biliary CEA, CA 19-9, VEGFR-3, and TAC tests were analyzed, statistics were obtained, and significance was defined as p<0.05. Results: Mean age was 54.9±16.4 for the benign and 54.2±19.6 for the malignant group (p=0.89). Head of pancreas cancer (18.2%), cholangiocarcinoma (11.4%) and choledochal stone (48%) were the most common etiologies. The area under the curve (AUC)s by ROC analysis of serum/biliary CA 19-9, VEGFR-3, and TAC and serum CEA were 0.701/0.616, 0.622/0.663, 0.602/0.581, and 0713, respectively. Serum TAC had higher sensitivity (61.1%) and CEA had lower sensitivity (42.7%), whereas CEA had higher specificity (89.9%) and TAC had lower specificity (60.5%). In biliary tumor markers, CA 19-9 had higher sensitivity (74%) and VEGFR-3 had lower sensitivity (56.2%); however, VEGFR-3 had higher specificity (79.1%) and CA 19-9 had lower specificity (34.1%). Additionally, combination of serum CEA (p<0.001), CA 19-9 (p<0.001), VEGFR-3 (p<0.001), and biliary CA 19-9 (p=0.028) markers achieved 95% estimation probability, and the sensitivity, specificity, and accuracy were 88.5%, 45.7%, and 64%, respectively. Conclusion: Serum and biliary CEA, CA 19-9, VEGFR-3, and TAC tests would not be useful in the differentiation between malignant and benign biliary obstructions.

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Antioxidant Status and Oxidative Stress Markers in Pancreatic Cancer and Chronic Pancreatitis

Abstract: Reduced antioxidant defense system capacity and increased markers of oxidative stress were found in PC and CP. PON1-L and CAT activities, along with ox-LDL/LDL levels, were the independent factors differentiating the patients with PC from the patients with CP.

Cited by 74 publications

References 41 publications

Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions

Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions

Carvacrol exhibits anti-oxidant and anti-inflammatory effects against 1, 2-dimethyl hydrazine plus dextran sodium sulfate induced inflammation associated carcinogenicity in the colon of Fischer 344 rats

Roles of serum and biliary CEA, CA19-9, VEGFR3, and TAC in differentiating between malignant and benign biliary obstructions

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