A Study of Salty Processed Food Consumption Pattern among Different Ethnic Group in Patient with Gastric Cancer

Gastric cancer is the fourth most frequently occurring malignancy, after lung, breast and colorectal cancer, and the second most common cause of death from cancer worldwide. The global incidence of gastric cancer shows wide geographic variation with a 15-20 fold difference between high and low incidence region. Therefore the prevention of gastric cancer represents one of the most important aspects of any cancer control strategy around the world. From the hospital based data in Nepal gastric cancer is the third most common cancer in males and the sixth common cancer in females. An observational hospital based descriptive study was carried out in the Oncology Unit of (NMCTH) from 2013-2018 on relationship between salty processed food consumption and increased possibility of development of gastric cancer in different ethnic groups of Nepal. Fifty-four diagnosed gastric cancer patients were enrolled and their dietary habits were extensively looked into. Of these 55.6% (30) were males and 44.4% (24) were females. The patient’s age ranged between 25-75 years and the peak incidence was in age group 41-60 years. The habit of consumption of smoked meat was higher (77.8%) than the consumption of packed food and fermented food. Tibeto-mongoloid ethnicity was found to have more prevalence (64.8%) to gastric cancer. The common site of presentation of gastric cancer was at the antrum (44.4%) and tubular adenocarcinoma was the most common type. It was the Tibeto-mongoloids whose food habit pattern comprised of major consumption of salty processed food and having more preference for salty processed food in daily life had increased high risk of gastric cancer than the other ethnic groups. This concludes that food consumption pattern play a critical role in the incidence of gastric cancer and dietary modification to reduce salt and salted food is a practical strategy with which gastric cancer risk can be prevented in these high risk ethnic group of Nepal.</jats:p

Abstract 17327: Ischemic Skeletal Muscle From Patients With Peripheral Arterial Disease Displays Marked Desialylation of Cell Surface Glycans: Implications for Ischemia-Targeted Gene Therapy

Introduction: Ischemic skeletal muscle is preferentially targeted after IV injection of AAV9 in mouse models of hind-limb ischemia (HLI). Ischemia is known to induce desialylation of cell surface glycans, unmasking the cellular receptor for AAV9 and resulting in significantly higher levels of selective gene expression in ischemic vs non-ischemic muscle. To assess clinical relevance, we compared the differential distribution of sialylated and desialylated cell surface glycans in skeletal muscle biopsies from peripheral arterial disease (PAD) patients and normal controls. Methods: Gastrocnemius (GA) muscle samples from PAD patients and normals (n=29 each) were biopsied under IRB-approved protocols. Muscle sections were stained using the lectins MAL-I and ECL. MAL-I binds to α2,3-sialylated glycans whereas ECL binds to desialylated galactose residues on cell surface glycans. Lectins were labeled with Streptavidin-Alexa-488 (red) for MAL-I and SA-555 (green) for ECL, and visualized using fluorescence microscopy. Quantification of mean fluorescence signal intensity of lectin staining was performed on each section. Results: Visually, MAL-I staining was markedly higher and ECL staining lower in non-ischemic GA from normals when compared to ischemic GA from PAD patients (Figure). The ratio of MAL-I to ECL integrated fluorescence intensity in the ischemic muscles from PAD patients (1.13 ± 0.13) was significantly lower than the same ratio in non-ischemic muscles from normals (1.58 ± 0.14, p&lt;0.02). Conclusions: Desialylation of cell surface glycans is significantly higher in ischemic skeletal muscle from PAD patients, consistent with previous work in a mouse model of HLI. This desialylation can potentially be exploited to treat human PAD with gene therapy, since these desialylated cell surface glycans serve as cell surface receptors for AAV9 and provide for efficient and selective gene transfer to ischemic skeletal muscle following systemic or local delivery. </jats:p

Adeno-associated virus serotype 9-mediated overexpression of extracellular superoxide dismutase improves recovery from surgical hind-limb ischemia in BALB/c mice

ObjectiveNeovascularization is a physiologic repair process that partly depends on nitric oxide. Extracellular superoxide dismutase (EcSOD) is the major scavenger of superoxide. It is an important regulator of nitric oxide bioavailability and thus protects against vascular dysfunction. We hypothesized that overexpression of EcSOD in skeletal muscle would improve recovery from hind-limb ischemia.MethodsAdeno-associated virus serotype 9 (AAV9) vectors expressing EcSOD or luciferase (control) from the cytomegalovirus promoter were cross-packaged into AAV9 capsids and injected intramuscularly into the hind-limb muscles (1 × 1011 viral genomes/limb) of 12-week-old mice. Ischemia was induced after intramuscular injections. Laser Doppler was used to measure limb perfusion on days 0, 7, and 14 after injection. Values were expressed as a ratio relative to the nonischemic limb. EcSOD expression was measured by Western blotting. Capillary density was documented by immunohistochemical staining for platelet endothelial cell adhesion molecule. Apoptosis was assessed by terminal deoxynucleotide transferase-mediated biotin-deoxy uridine triphosphate nick-end labeling and necrosis was visually evaluated daily.ResultsEcSOD expression was twofold upregulated in EcSOD treated vs control ischemic muscles at day 14. Capillary density (capillaries/fiber) was 1.9-fold higher in treated (1.65 ± 0.02) vs control muscle (0.78 ± 0.17, P < .05). Recovery of perfusion ratio at day 14 after ischemia was 1.5-fold greater in EcSOD vs control mice (P < .05). The percentage of apoptotic nuclei was 1.3% ± 0.4% in EcSOD-treated mice compared with 4.2% ± 0.2% in controls (P < .001). Limb necrosis was also significantly lower in EcSOD vs control mice.ConclusionAAV9-mediated overexpression of EcSOD in skeletal muscle significantly improves recovery from hind-limb ischemia in mice, consistent with improved capillary density and perfusion ratios in treated mice.Clinical RelevanceAtherosclerosis remains a major cause of morbidity and mortality in the Western world. Extensive research has been conducted to attempt to harness the ability to facilitate the growth of blood vessels to limit the complications that follow an arterial occlusion. In no area of medicine is this needed greater than in peripheral arterial disease (PAD), where patients continue to experience high rates of poor wound healing and amputation. Gene therapy has been attempted in humans, with mixed results to date. Our study used a preclinical model of surgically induced hind-limb ischemia in a strain of mice that have a low rate of endogenous perfusion recovery from ischemia and a high risk of necrosis. We used an adeno-associated virus serotype 9 (AAV9) as the vector to deliver the gene expressing extracellular superoxide dismutase (EcSOD). Intramuscular EcSOD demonstrated a beneficial effect in this preclinical model. The AAV9 was able to induce high levels of gene expression without inducing detectable inflammation. This study may serve as a foundation for the future investigation of EcSOD, AAV9, or both, in PAD