Role of Branched-chain Amino Acid Metabolism in Tumor Development and Progression

Branched-chain amino acids (BCAAs), isoleucine, leucine and valine, are essential amino acids with vital roles in protein synthesis and energy production. We reviewed the fundamentals of BCAA metabolism in advanced cancer patients. BCAAs and various catabolic products act as signalling molecules, which activate mechanisms ranging from protein synthesis to insulin secretion. Recently, BCAA metabolism has been suggested to contribute to cancer progression. Of particular interest is the modulation of the mTOR activity by BCAAs. There are likely multiple pathways involved in BCAA metabolism implicated in carcinogenesis. Understanding the mechanism(s) underlying altered BCAAs metabolism will significantly advance the current understanding of nutrient involvement in carcinogenesis and direct future studies to unravel the significance of BCCA metabolites in tumor development and progression.

Efficacy of Cereal-based Oral Nutrition Supplement onNutritional Status, Inflammatory Cytokine Secretion andQuality of Life in Cancer Patients under Cancer Therapy

A rapid increase in cancer incidence accompanied by aging population requires evidence-based supportive cancer care practices.Cancer therapies often accompany adverse events which induce malnutrition and declined quality of life. We conducted an 8-weeknon-randomized clinical trial to evaluate efficacy of cereal-based oral nutritional supplement (ONS) intervention on nutritional status,quality of life and inflammatory responses in cancer patients undergoing cancer therapy with 5% < weight loss. The study included34 pateints (24 in control group, 10 in intervention group) with 15 drop-outs. ONS used in this intervention contained 0.5% arabinoxylan-rich fermented rice bran powder and 5.5% black rice powder as active ingredients in a regular cereal-based formula. Resultsshowed that ONS intervention for 8 weeks did not show significant improvement in blood biomarkers of nutritional status or patient-generated subjective global assessment scores. However, 8-week of intervention showed reduced interleukin (IL)-6 and IL-1bsecretion in lipopolysaccharide-stimulated peripheral blood mononuclear cells while IL-12p70 level was increased. For health-relatedquality of life (HRQoL) indices, emotional functioning and fatigue symptoms were improved after 4 weeks only in the interventiongroup although no difference was found at week 8. These results suggest that ONS intervention may improve chronic inflammatorystatus and HRQoL indices (at week 4) in cancer patients receiving treatments.

Risk Factors for Vitamin D, Zinc, and Selenium Deficiencies in Korean Patients with Inflammatory Bowel Disease

BACKGROUND/AIMS: Studies on the micronutrient status of Asian patients with inflammatory bowel disease (IBD) are scarce. We evaluated the prevalence of micronutrient deficiency and verified the risk factors for micronutrient deficiency in Korean patients with IBD. METHODS: We measured the serum levels of 25-hydroxyvitamin D3 [25-(OH)D], zinc, and selenium to analyze the clinical risk factors for micronutrient levels below the reference values. In addition, we compared the 25-(OH)D levels of patients with IBD to those of age- and sex-matched healthy controls. RESULTS: Among the 83 patients, 74 (89.2%) had suboptimal serum 25-(OH)D levels. The mean plasma 25-(OH)D level in patients with IBD was significantly reduced compared to that of the healthy controls (12.3±6.2 ng/mL vs 20.0±6.7 ng/mL; p<0.001). The proportions of patients with lower serum zinc and selenium levels were 39.0% and 30.9%, respectively. Female sex (p=0.012) and Crohn’s disease (p=0.012) were associated with vitamin D deficiency. Patients younger than 40 years were at increased risk for zinc deficiency (p=0.045). Female sex (p=0.015) and low serum albumin level (<3.3 g/dL) (p=0.047) were risk factors for selenium deficiency. CONCLUSIONS: Many Korean patients with IBD have vitamin D, zinc, and selenium deficiencies, suggesting the necessity for monitoring levels of these micronutrients.

High-fat Diet Accelerates Intestinal Tumorigenesis Through Disruption Intestinal Cell Membrane Integrity

There is an error in a grant number in Acknowledgements.

High-fat Diet Accelerates Intestinal Tumorigenesis Through Disrupting Intestinal Cell Membrane Integrity

BACKGROUND: Excess energy supply induces chronic low-grade inflammation in association with oxidative stress in various tissues including intestinal epithelium. The objective of this study was to investigate the effect of high-fat diet (HFD) on intestinal cell membrane integrity and intestinal tumorigenesis in ApcMin/+ mice. METHODS: Mice were fed with either normal diet (ND) or HFD for 12 weeks. The number of intestinal tumors were counted and biomarkers of endotoxemia, oxidative stress, and inflammation were determined. Changes in intestinal integrity was measured by fluorescein isothiocyanate (FITC)-dextran penetration and membrane gap junction protein expression. RESULTS: HFD group had significantly higher number of tumors compared to ND group (P < 0.05). Blood total antioxidant capacity was lower in HFD group, while colonic 8-hydroxy-2'-deoxyguanosine level, a marker of oxidative damage, was higher in HFD group compared to that of ND group (P < 0.05). The penetration of FITC-dextran was substantially increased in HFD group (P < 0.05) while the expressions of membrane gap junction proteins including zonula occludens-1, claudin-1, and occludin were lower in HFD group (P < 0.05) compared to those in ND group. Serum concentration of lipopolysaccharide (LPS) receptor (CD14) and colonic toll-like receptor 4 (a LPS receptor) mRNA expression were significantly higher in HFD group than in ND group (P < 0.05), suggesting that significant endotoxemia may occur in HFD group due to the increased membrane permeability. Serum interleukin-6 concentration and myeloperoxidase activity were also higher in HFD group compared to those of ND group (P < 0.05). CONCLUSIONS: HFD increases oxidative stress disrupting intestinal gap junction proteins, thereby accelerating membrane permeability endotoxemia, inflammation, and intestinal tumorigenesis.

The Efficacy of Oral Nutritional Intervention in Malnourished Cancer Patients: a Systemic Review

Cancer is currently a leading cause of deaths worldwide and the number of new cases is growing rapidly in both, developed and developing countries. Nutritional management during and after cancer treatment affects treatment efficacy and patient quality of life (QOL). This review systemically examined the effect of oral nutritional interventions on nutritional and clinical outcomes in cancer patients. We especially focused on outcomes such as nutritional status indices, immune-associated biochemical markers, and QOL assessments to provide insights on the applicability of different outcomes. A total of 28 papers were selected for systematic review. The nutritional composition of oral nutritional supplements (ONS), outcome measures, and efficacy of the oral nutritional interventions were summarized and discussed. Most ONS contain 1 or more functional components in addition to basic nutrients. Each study used various outcome measures and significant efficacy was observed for a limited number of measures. Nutritional status indices, QOL measures, and the duration of hospital stay improved in about 40% of the studies. One or more markers of immune function and inflammatory responses were improved by ONS in 65% of the selected studies. These results suggest that appropriate use of ONS may be an ideal way to improve treatment efficacy; however, additional intervention trials are required to confirm these findings.

Chemopreventive Action of Anthocyanin-rich Black Soybean Fraction in APC(Min/+) Intestinal Polyposis Model

BACKGROUND: Anthocyanins have been shown to inhibit cancer cell growth by suppressing oxidative stress and inflammatory responses. The purpose of this study was to investigate the effects of an anthocyanin-rich extract (AE) from black soybean coat on intestinal carcinogenesis. METHODS: APC(Min/+) mice were fed a diet of 0.2% or 0.5% AE for 7 weeks. We analyzed the number of intestinal tumors, oxidative stress and inflammatory markers associated with beta-catenin and cytosolic phospholipase A2 (cPLA2) signals. The number of intestinal tumors, and cellular expression of beta-catenin were determined. RESULTS: The number of intestinal tumors was significantly lower in mice fed a 0.5% AE diet compared to those of the other groups. Cytosolic beta-catenin expression was significantly decreased in the AE supplemented groups compared to that of the control animals. In addition, mucosa expression of cyclooxygenase-2 and cPLA2 were also significantly decreased in the 0.5% AE group, by 32% and 62%, respectively, compared to the control group. CONCLUSIONS: These results suggest that dietary AE reduced the development of intestinal tumors, possibly through the ability to suppress oxidative stresses, decreasing inflammatory responses mediated by beta-catenin associated signals.

Erratum: The Palatability of Cereal Based Nutritional Supplements in Cancer Patients

We would like to correct the affiliation for the first author.

Estrogen deprivation and excess energy supply accelerate 7,12-dimethylbenz(a)anthracene-induced mammary tumor growth in C3H/HeN mice

BACKGROUND/OBJECTIVES: Obesity is a risk factor of breast cancer in postmenopausal women. Estrogen deprivation has been suggested to cause alteration of lipid metabolism thereby creating a cellular microenvironment favoring tumor growth. The aim of this study is to investigate the effects of estrogen depletion in combination with excess energy supply on breast tumor development. MATERIALS/METHODS: Ovariectomized (OVX) or sham-operated C3H/HeN mice at 4 wks were provided with either a normal diet or a high-fat diet (HD) for 16 weeks. Breast tumors were induced by administration of 7,12-dimethylbenz(a)anthracene once a week for six consecutive weeks. RESULTS: Study results showed higher serum concentrations of free fatty acids and insulin in the OVX+HD group compared to other groups. The average tumor volume was significantly larger in OVX+HD animals than in other groups. Expressions of mammary tumor insulin receptor and mammalian target of rapamycin proteins as well as the ratio of pAKT/AKT were significantly increased, while pAMPK/AMPK was decreased in OVX+HD animals compared to the sham-operated groups. Higher relative expression of liver fatty acid synthase mRNA was observed in OVX+HD mice compared with other groups. CONCLUSIONS: These results suggest that excess energy supply affects the accelerated mammary tumor growth in estrogen deprived mice.

Carnosic Acid Inhibits Lipid Accumulation in 3T3-L1 Adipocytes Through Attenuation of Fatty Acid Desaturation

BACKGROUND: Excess body fat accumulation contributes to the development of metabolic disorders that can cause adverse health effects. Carnosic acid (CA), a major bioactive component of rosemary (Rosemarinus officinalis), has been suggested to possess anti-adipogenic properties. The present study was conducted to elucidate the mechanism underlying the anti-adipogenic effects of CA. METHODS: 3T3-L1 pre-adipocytes were treated with CA (0.1, 1, and 10 muM) from day 0 to day 8 of differentiation. On day 8, biochemical markers of lipid accumulation and the degree of fatty acid desaturation were measured. RESULTS: Oil Red O staining results, triglyceride (TG) accumulation, and glycerol 3-phosphate dehydrogenase activity suggested that CA significantly inhibited lipid accumulation in 3T3-L1 adipocytes. CA significantly decreased mRNA expression of peroxisome proliferator-activated receptor-gamma, sterol regulatory element-binding protein 1, and CCAAT/enhancer binding protein-alpha in a dose-dependent manner. Moreover, it decreased the ratio of both C16:1/C16:0 and C18:1/C18:0, with reduced expression of stearoyl CoA desaturase 1 mRNA and protein. CONCLUSIONS: These results suggest that CA efficiently suppressed adipogenesis in 3T3-L1 adipocytes and its action, at least in part, is associated with the downregulation of adipogenesis-related genes and the fatty acid composition of TG accumulated in adipocytes.

Association Between Usual Vitamin K Intake and Anticoagulation in Patients Under Warfarin Therapy

This study aimed to explore the correlation between usual vitamin K intake and response to anticoagulant therapy among patients under warfarin therapy. We conducted a retrospective survey of patients (n = 50) on continuous warfarin therapy. Clinical information and laboratory parameters were sourced from medical records. Anticoagulant effect was evaluated by using the percent time in therapeutic range (TTR) and the coefficient of variation (CV) of International normalized ratio (INR). Dietary vitamin K intake was assessed using a semi-quantitative food frequency questionnaire that has been developed for the purpose of assessing dietary intake of vitamin K. A total of 50 patients aged between 21 and 87 years were included in the study. The mean vitamin K intake was 262.8 +/- 165.2 microg/day. Study subjects were divided into tertiles according to their usual vitamin K intake. The proportion of men was significantly higher in second and third tertile than first tertile (p = 0.028). The mean percent TTR was 38.4 +/- 28.4% and CV of INR was 31.8 +/- 11.8%. Long-term warfarin therapy group (> or = 3 years) had a higher percentage of TTR as compared to the control group ( 0.05). In conclusion, no significant association was observed between usual vitamin K intake and anticoagulant effects. Further studies are required to consider inter-individual variability of vitamin K intake. Development of assessment tools to measure inter-individual variability of vitamin K intake might be helpful.

The Palatability of Cereal Based Nutritional Supplements in Cancer Patients

Recently, it is reported that intervention of oral nutritional supplement improves the nutritional status of cancer patients, and the effectiveness is affected by the sensory preference of cancer patients on the oral nutritional supplement. However, the variety of oral nutritional supplement is extremely limited and the number of patient's benefits from using the products are restricted mostly due to sensory dislikes. The objective of this study was to provide sensory preference score of trial manufactured products with different accessory ingredients to maximize the use of oral nutritional supplements. Cancer patients (n = 30) and age, sex-matched healthy volunteers (n = 30) participated in the sensory assessments (taste, flavor, viscosity, color and overall preference) of three types of oral supplements (cereal base, cereal base+herb and cereal base+fruit) and a control supplement product with scorched cereal flavor, a top seller in current Korean market. Results indicate that the cancer patients' overall preference was significantly higher for the control supplement, and fruit added supplement was preferred over plain cereal and herb added products, although the difference was insignificant. However, there was no significant preference difference for the supplements among the control group for all sensory factors. These results suggest that cancer patients are more sensitive to sensory preferences compared to the control group, and the patients prefer the flavor of cooked cereal which is a staple food in Korea.

Prognostic Role of Interleukin-6, Interleukin-8, and Leptin Levels According to Breast Cancer Subtype / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Inflammation within the tumor microenvironment has been reported to show an association with poor prognosis in breast cancer. However, the associations may differ according to breast cancer subtype. In this study, we investigated the association between inflammation-related markers and breast cancer recurrence according to patients' tumor subtypes. MATERIALS AND METHODS: This prospective study included 240 patients who underwent surgery for management of newly diagnosed breast cancer. Levels of inflammation-related markers (interleukin [IL]-1beta, IL-6, IL-8, monocyte chemoattractant protein-1 [MCP-1], leptin, and adiponectin) were measured at diagnosis, and the associations between these markers and breast cancer recurrence during a six-year follow-up period were examined using the Kaplan-Meier statistical method. RESULTS: Overall, inflammation-related markers showed no association with breast cancer recurrence. However, when data were stratified by tumor subtype, higher levels of some mediators showed an association with poor prognosis among patients with particular subtypes. Compared to patients without recurrence, patients with recurrence had higher levels of circulating IL-6 (p=0.024) and IL-8 (p=0.016) only among those with HER2- tumors and had higher levels of leptin (p=0.034) only among those with estrogen receptor (ER)+/progesterone receptor (PR)+ tumors. Results of survival analyses revealed an association of high levels of IL-6 (p=0.016) and IL-8 (p=0.022) with poor recurrence-free survival in patients with HER2- tumors. In addition, higher leptin levels indicated shorter recurrence-free survival time only among patients with ER+/PR+ tumors (p=0.022). CONCLUSION: We found that certain cytokines could have a differential prognostic impact on breast cancer recurrence according to breast cancer subtype. Conduct of additional large studies will be required in order to elucidate the precise roles of these cytokines in breast cancer progression.

Evaluation of Adiposity-Related Biomarkers as Metabolic Syndrome Indicators

Recent studies have suggested a relationship of the increased circulating adipokines and inflammatory cytokine, and the risk of metabolic syndrome (MetS). The objective of this study was to identify adiposity-related factors that reflect MetS in order to establish early intervention targets. We performed a cross-sectional study which included 108 MetS subjects and 91 controls. Blood adiponectin, leptin, vascular-, and intercellular adhension molecules (VCAM, ICAM), monocyte chemoattractant protein 1 (MCP1), high-sensitivity C-reactive protein (hsCRP), oxidized LDL (oxLDL), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured. The correlation analysis indicated that the MetS score (sum of the number of MetS risk factors) had an inverse relationship with adiponectin (p < 0.0001), and positive correlations with leptin (p < 0.05), ICAM (p < 0.01), MCP1 (p < 0.05), oxLDL (p < 0.05), TNF-alpha (p < 0.0001), IL-6 (p < 0.05) and hsCRP (p < 0.01). In multivariate logistic regression analyses, plasma triglyceride (TG) was independently associated with adiponectin, ICAM and TNF-alpha with the standardized beta coefficients of -0.213, 0.197, and 0.193, respectively. Plasma HDL-cholesterol was independently associated with ICAM and hsCRP with the standardized beta coefficients of -0.150 and -0.173. Adiponectin, TNF-alpha, and hsCRP were the most proximate markers reflecting MetS. Among MetS components, TG and HDL-cholesterol concentrations displayed the relationship with inflammatory markers measured in this study.

Clinical Nutrition Research: Toward the Prevention and Control of Noncommunicable Diseases

No abstract available.

Consumption of Sugar-Sweetened Beverages and Blood Pressure in the United States: The National Health and Nutrition Examination Survey 2003-2006

High sugar intake has been suggested to be related to hypertension. To examine the associations between intakes of sugar and sugar-sweetened beverages (SSBs) and the prevalence of hypertension, we used the US National Health and Nutrition Examination Survey (NHANES) 2003-2006. A total of 3,044 participants aged > or =19 years were included. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariate logistic regression model. Prevalent hypertension cases were defined as systolic blood pressure (SBP) of > or =140 mmHg or diastolic blood pressure (DBP) of > or =90 mmHg. In the multivariate adjusted models, we observed no association between sugar consumption and the prevalence of hypertension. In the model where we adjusted for age, gender, NHANES period and BMI, those who consumed > or =3 times per day of sugar-sweetened beverages had an OR of 1.87 (95% confidence interval, CI = 1.06-3.26) for the prevalence of hypertension compared with those who consumed or =3 times per day of sugar-sweetened beverages compared to the <1 time per month (p for trend = 0.33). In conclusion, we found that sugar consumption was not associated with the prevalence of hypertension, however there was suggestion that high sugar-sweetened beverage consumption was associated with high prevalence of hypertension in the US.

Establishment of Korean Dietary Guidelines for Cancer Prevention

BACKGROUND: As a leading cause of death in Korea, cancer is known to be related to lifestyle including diet. In 2007, the World Cancer Research Fund announced 10 evidence-based guidelines for reducing the number of cancers. The purpose of this paper was to produce guidelines specific to and relevant to the people of Korea. METHODS: Ranging over 6 categories, 15 dietary factors known to be associated with cancers were selected after reviewing the results of relevant researches including Korean subjects and evidence-based research documents regarding the relationships between cancer and diet. The levels of intake of these selected dietary factors by Koreans were compared to the established dietary guidelines and detailed practices for cancer prevention. RESULTS: The Korean dietary guidelines for cancer prevention consists of 8 detailed recommendations along with multiple specific practices based on the analyses of data and documents on weight and intake of cereals, fruits, vegetables, meat, salt, dairy products, alcohol, and nutrient supplements. CONCLUSIONS: The Korean dietary guidelines for cancer prevention were established based on valid scientific approach by analyzing the most recent available data. For some dietary factors, however, sufficient analysis for intake levels in Koreans was not possible. Therefore, fundamental data for the establishment of national strategy and for guideline amendments for preventing cancers need to be gathered through the analyses of relationships between cause and deaths due to cancer, database reinforcement, additional research including Korean subjects, and assessment of usual intake.

Huge Gastric Schwannoma Characterized by a Gastric Ulcer During Endoscopy / 대한소화기내시경학회지

Gastric schwannomas are very rare mesenchymal tumors that can occur throughout the gastrointestinal tract, but are most commonly found in the stomach. The majority of patients have no symptoms, while others may complain of epigastric pain or upper gastrointestinal ulcer bleeding. Endoscopic examination of a gastric schwannoma commonly reveals a protrusive mass, but, as in this case, many types of ulceration can be observed with central necrosis. We report on a 62-year-old woman with endoscopic findings of 1 cm sized necrotizing ulceration and an 11 cm sized submucosal mass on radiological examinations. The patient underwent a wedge-shaped resection of the stomach and segmental resection of the transverse colon. Both histological and immunohistochemical staining revealed a gastric schwannoma.

Coconut-derived D-xylose affects postprandial glucose and insulin responses in healthy individuals

Metabolic alterations including postprandial hyperglycemia have been implicated in the development of obesity-related diseases. Xylose is a sucrase inhibitor suggested to suppress the postprandial glucose surge. The objectives of this study were to assess the inhibitory effects of two different concentrations of xylose on postprandial glucose and insulin responses and to evaluate its efficacy in the presence of other macronutrients. Randomized double-blind cross-over studies were conducted to examine the effect of D-xylose on postprandial glucose and insulin response following the oral glucose tolerance test (OGTT). In study 1, the overnight-fasted study subjects (n = 49) consumed a test sucrose solution (50 g sucrose in 130 ml water) containing 0, 5, or 7.5 g D-xylose powder. In study 2, the overnight-fasted study subjects (n = 50) consumed a test meal (50 g sucrose in a 60 g muffin and 200 ml sucrose-containing solution). The control meal provided 64.5 g of carbohydrates, 4.5 g of fat, and 10 g of protein. The xylose meal was identical to the control meal except 5 g of xylose was added to the muffin mix. In study 1, the 5 g xylose-containing solutions exhibited significantly lower area under the glucose curve (AUCg) and area under the insulin curve (AUCi) values for 0-15 min (P < 0.0001, P < 0.0001), 0-30 min (P < 0.0001, P < 0.0001), 0-45 min (P < 0.0001, P < 0.0001), 0-60 min (P < 0.0001, P < 0.0001), 0-90 min (P < 0.0001, P < 0.0001) and 0-120 min (P = 0.0071, P = 0.0016). In study 2, the test meal exhibited significantly lower AUCg and AUCi values for 0-15 min (P < 0.0001, P < 0.0001), 0-30 min (P < 0.0001, P < 0.0001), 0-45 min (P < 0.0001, P = 0.0005), 0-60 min (P = 0.0002, P = 0.0025), and 0-90 min (P = 0.0396, P = 0.0246). In conclusion, xylose showed an acute suppressive effect on the postprandial glucose and insulin surges.

Effects of Panicum miliaceum L. extract on adipogenic transcription factors and fatty acid accumulation in 3T3-L1 adipocytes

The dietary intake of whole grains is known to reduce the incidence of chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. To investigate whether there are anti-adipogenic activities in various Korean cereals, we assessed water extracts of nine cereals. The results showed that treatment of 3T3-L1 adipocytes with Sorghum bicolor L. Moench, Setaria italica Beauvois, or Panicum miliaceum L. extract significantly inhibited adipocyte differentiation, as determined by measuring oil red-O staining, triglyceride accumulation, and glycerol 3-phosphate dehydrogenase activity. Among the nine cereals, P. miliaceum L. showed the highest anti-adipogenic activity. The effects of P. miliaceum L. on mRNA expression of peroxisome proliferator-activated receptor-gamma, sterol regulatory element-binding protein 1, and the CCAAT/enhancer binding protein-alpha were evaluated, revealing that the extract significantly decreased the expression of these genes in a dose-dependent manner. Moreover, P. miliaceum L. extract changed the ratio of monounsaturated fatty acids to saturated fatty acids in adipocytes, which is related to biological activity and cell characteristics. These results suggest that some cereals efficiently suppress adipogenesis in 3T3-L1 adipocytes. In particular, the effect of P. miliaceum L. on adipocyte differentiation is associated with the downregulation of adipogenic genes and fatty acid accumulation in adipocytes.