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S57Vol. 211, No. 3S, September 2010 Surgical Forum Abstracts

eled before hybridization to Human Genome U133 2.0 PluseneChip array. Chip analysis was performed for significantly up-

egulated and/or downregulated genes, compared to controls, withicroarray software.

ESULTS: The 12 hour sample demonstrated numerous upregu-ated (�4 fold) and downregulated (�3 fold) genes. Please refer tohe included table for specific genes and change ratios.

ene Name Ratio p-Value

pregulated:Heme oxygenase (decycling) 1 16.96 0.00444DNA-damage-inducible transcript 3 6.3 0.00622Chemokine (C-X-C motif) ligand 3 6.08 0.03221Superoxide dismutase 2, mitochondrial 4.53 0.03353Heat shock 70kDa protein 9 (mortalin) 4.33 0.00124ownregulated:Zinc finger protein 488 4.32 0.04088Integrin, beta 8 4.03 0.01345Cytochrome P450, family 1, subfamily A 3.58 0.00029Dehydrogenase/reductase (SDR family) 3.15 0.01714

ONCLUSIONS: To our knowledge, this is the first genomic eval-ation of human cancer cells upon treatment with Pterostilbene.revious evidence of mitochondrial depolarization by Pterostilbenealidates findings of upregulated Heme Oxygenase, mitochondrialuperoxide dismutase 2, and Heat Shock 70kD Protein genes. Theehydrogenase/reductase (SDR Family), involved with redox reac-

ions, may play a role in mitochondrial reactive oxygen species am-lification under stress. This work confirms our previous in vitroindings and supports further evaluations of the pancreatic cancerellular response to Pterostilbene.

issue specific hypermethylation of diabeteselated gene in a type 2 diabetes mellitus ratodel undergoing Roux-en-Y gastric bypass

ederico J Serrot MD, Gonzalo Torres-Villalobo MD,athan Springer PhD, Bridget Slusarek RN, Sayeed Ikramuddin MDniversity of Minnesota, Minneapolis, MN

NTRODUCTION: Epigenetics is defined as heritable changes inene expression by differential methylation of regions that are notncoded directly within the DNA sequence of genes. Disruption ofpigenetic states can lead to the development of cancer and otheriseases. The Goto-Kakizaki (GK) rat is a lean diabetic animal with

mpaired insulin responsiveness to glucose. CDKN2A encodes pro-ein p16 which is a negative regulator of the cell cycle. Numeroustudies have implicated this gene to diabetes susceptibility. We hy-othesized that methylation of CDKN2A would be affected by bari-tric surgery as opposed to sham operation.

ETHODS: Six GK rats underwent either a Roux-en-Y Gastric By-

ass (n � 3) or Sham surgery (n�3). Liver, adipose and muscle tissue m

amples were harvested pre and post surgery and were assessed forethylation using direct bisulfite sequencing.

ESULTS: None of the studied regions showed differential meth-lation in samples taken before and after bariatric surgery in any ofhe tissues under study. However, the studied region in theDKN2A gene was tissue-specific differentialy methylated. Muscle

amples before and after surgery showed significantly higher meth-lation (averaged amplicon methylation (AAM) � 12 %) than fatAAM�2%) and liver (AAM�0%). Lack of differences among an-mals showed that there were no significant differences in biologicaleplicates.

ONCLUSIONS: To our knowledge, this study is the first reportingissue-specific differential methylation in CDKN2A gene. Differ-ntly to the comprehensive reports in cancer, little is known on theole of the epigenetic regulation of the CDKN2A gene in diabetes.urther studies need to be done.

esistin expression correlates with steatohepatitisn obese patientslaire Edwards MD, A Katharine Hindle MD,atricia Latham MD, Sidney Fu MD, PhD, Fredrick Brody MDhe George Washington University Medical Center, Washington,C

NTRODUCTION: Morbidly obese patients are at risk for non-lcoholic steatohepatitis (NASH) even in the absence of risk factorsor liver disease. Unfortunately, NASH is usually not clinically evi-ent, and a definitive, non-invasive test for NASH does not exist.esistin, a cytokine originating from adipose tissue, is involved in

nsulin resistance and initiates pro-inflammatory signaling from he-atic stellate cells. This study explores the relationship between resis-in expression and liver pathology in bariatric surgery patients.

ETHODS: Blood samples from 30 patients undergoing bariatricurgery were collected. Total RNA was extracted and cDNA wasynthesized. Quantitative RT-PCR was used to quantify relative genexpression using 18s rRNA gene as an internal control. Wedge liveriopsies from these patients were sectioned and stained. Using areviously published scoring method, biopsies were assigned an over-ll NASH severity score and subscores for steatosis, inflammation,nd fibrosis. Results were analyzed using Student’s t-test.

ESULTS: Resistin mRNA levels ranged from 2.5 to 45. A group ofour patients with very high resistin expression (� 25) was identified.hese patients had a significantly higher average NASH score com-ared to the rest of the group (8.00 vs. 4.27, p�0.01). Steatosis andnflammation score were also significantly higher in this groupp�0.05 for both comparisons). Fibrosis score did not significantlyiffer.

ONCLUSIONS: In morbidly obese patients, high resistin expres-ion in serum is associated with hepatic steatosis and inflammation,ut not with fibrosis. The development of elevated resistin expression

ay represent a link between obesity and the onset of steatohepatitis.