Plasma Amino Acid Profiles Research Articles

Abstract 413: Involvement of myeloid derived suppressor cells (MDSC) in the changes of plasma amino acid profiles in cancer disease

Abstract Although maintained in healthy human, it is well known that plasma amino acid profiles are changed in various pathologic conditions, including liver disorder and cancer. We have previously reported the potential use of plasma amino acid profiling as diagnosis for several cancer disease. However, some questions remained for the mechanisms. The changes in plasma amino acid profiles in tumor disease were regulated by a lot of factors, including metabolic changes of tumors and immune cells. In this study, we focused on the role of immune cells, especially myeloid derived suppressor cells (MDSC). MDSC are characterized as immature myeloid cells that are precursors of dendritic cells, macrophages, and/or granulocytes, they are considered to accumulate in the blood, lymph nods, and at tumor sites in most patients and experimental animals with cancer and inhibit anti-tumor inflammation. Therefore we hypothesized that MDSC were involved in the changes in plasma amino acid profiles in tumor disease. To test our hypothesis, we employed C57BL/6 mice tumor model in which Lewis lung carcinoma (3LL) was injected subcutaneously. Using flow cytometry analysis, a significant percentage of MDSC were detected in spleens of tumor-bearing mice as compared to control normal mice. To assess the role of MDSC in the changes in plasma amino acid profile, we eliminated MDSC from the tumor-bearing mice by inducing apoptosis cell death on MDSC selectively in vivo. Flow cytometry results showed a significant decrease in the percentage of CD11b+ Gr1+ cells in splenocytes derived from MDSC deleted tumor-bearing mice as compared to tumor-bearing mice. To study the immunogenic effects of the MDSC deletion on the tumor-bearing mice, we performed histological analysis (H&E staining) and extensive areas of inflammation within 3LL subcutaneous tumors were observed after the MDSC deletion. In addition, we investigated the effects of the MDSC deletion on the percentage of splenic T cell subpopulations by Flow cytometry. The percentage of CD4+ and CD8+ T cells were increased in spleens of MDSC deleted tumor-bearing mice compared to untreated tumor-bearing mice. To evaluate the effects of the MDSC depletion on the plasma amino acid profiles, plasma samples were collected from normal mice, tumor-bearing mice, and MDSC deleted tumor-bearing mice. Plasma amino acid concentration were measured by LC-MS. The MDSC deletion significantly changed the concentrations of some amino acids in plasma compared to the untreated tumor-bearing mice and normal mice. These changes in plasma amino acid concentrations were partially impeded by adoptive transfer of MDSC from tumor-bearing mice. Altogether, these results suggest that MDSC may be involved in the changes in plasma amino acid profiles in tumor disease. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 413. doi:10.1158/1538-7445.AM2011-413

Abstract 3784: HMGB1 affects plasma amino acid profiles in colon carcinogenesis

Abstract Alteration of the plasma free amino acid profile was reported to be a potential marker of colorectal cancer and breast cancer. The plasma amino acid profile has been reported as a relevant marker for early detection of colorectal cancer (Okamoto N et al. Int J Med Med Sci, 2009). In the present study, we examined the plasma amino acid profile as a marker for evaluating colon cancer risk. The amino acid profiles were examined in the mouse plasma using DMH-induced C57BL6 mouse colon carcinogenesis model. The plasma amino acid profiles of DMH-treated mice were different from that in control mice. Importantly, the plasma amino acid profile at procarcinogenic phase was also distinguished from the control. We focused on HMGB1, which was timely increased in serum and colon mucosa of the DMH-treated mice. In HMGB1-adeministrated mice, the plasma amino acid profiles showed a resemble pattern with that in the procarcinogenic phase mice. Decrease of most amino acids in the liver and skeletal muscle suggested an increase of catabolism in HMGB1-treated mice. In the mouse liver and muscle tissues, HMGB1 decreased pyruvate kinase M1 expression, and tetrazolium desoxydation, whereas lactate production was not increased. HMGB1 decreased phosphorylation levels of mTOR and increased protein levels of Beclin1 and LC3 in mouse liver and muscle tissue, whereas a mitochondrial marker, Diablo was not affected. Inhibitor of p38 MAPK abrogated HMGB1-induced autophagy signals. These findings suggest that HMGB1 affects energy production in mitochondria and activates autophagy signals, which might induce protein degradation and subsequent alteration of plasma amino acid profiles. The change of the plasma amino acid profiles might be a key finding detecting procarcinogenic status of the colon. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3784. doi:10.1158/1538-7445.AM2011-3784

Abstract LB-296: Involvement of T-cell immunity in changes in the plasma amino acid profiles of patients with colorectal cancer

Abstract Metabolic changes in patients with various disorders, including liver disease and cancer, lead to alterations in amino acid balance, and plasma amino acid profiles can be used to discriminate between non-malnourished patients with cancer and healthy individuals. Not with standing, the mechanisms of amino acid imbalance are not well understood. In patients with cancer, various factors including metabolic changes in the tumor itself and immune responses may affect plasma amino acid levels. To investigate involvement of the immune system, we measured plasma amino acid levels in an orthotopic transplant model of colon cancer established in both conventional BALB/c mice and athymic BALB/c nude mice (T-lymphocyte-deficient mice). CT26 colon cancer cells (murine colon cancer cell line) were implanted into the cecal wall of the BALB/c mice (n=10) and nude mice (n=10). Plasma samples were collected from the tumor-bearing mice at 7 and 14 days after transplantation, and changes in plasma amino acid profiles were compared. Plasma was also collected from mice that underwent sham operation (control mice, n=10). Plasma amino acid concentrations were measured by LC/MS/MS. The plasma concentrations of several amino acids changed significantly in tumor-bearing mice compared to concentrations in control mice. Although cells from the same line were injected into the cecal wall of BALB/c mice and nude mice, a difference was noted in the change in plasma amino acid levels. Plasma Val, Ile, Leu, and Met levels decreased in BALB/c mice but increased in nude mice. There was no difference in the amino acid profile of CT26 tumor tissues between BALB/c mice and nude mice. We then injected antiCD3-antibody into the peritoneal cavity of tumor-bearing BALB/c mice (n=5) to eliminate T-cell function. We also injected IgG into tumor-bearing BALB/c mice (n=5) for control. The pattern of change in amino-acid profiles differed between the two groups of mice. Our findings suggest that T-lymphocyte-mediated immunoreactions are involved in changes in the plasma amino acid profile in patients with colorectal cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-296. doi:10.1158/1538-7445.AM2011-LB-296

Long-Term Enteral Arginine Supplementation in Rats with Intestinal Ischemia and Reperfusion

The effects of short-term enteral arginine supplementation on intestinal ischemia-reperfusion (IR) injury have been widely studied, especially the ischemic preconditioning supplementation. The aim of this study was to investigate the effects of long-term intra-duodenal supplementation of arginine on intestinal morphology, arginine-associated amino acid metabolism, and inflammatory responses in rats with intestinal IR. Male Wistar rats with or without three hours of ileal ischemia underwent duodenal cannulation for continuous infusion of formula with 2% arginine or commercial protein powder for 7 d. The serological examinations, plasma amino acid and cytokine profiles, and intestinal morphology were assessed. Intestinal IR injury had significant impacts on the decreases in circulating red blood cells, hemoglobin, ileum mass, and villus height and crypt depth of the distal jejunum. In addition, arginine supplementation decreased serum cholesterol and increased plasma arginine concentrations. In rats with intestinal IR injury, arginine supplementation significantly decreased serum nitric oxide, plasma citrulline and ornithine, and the mucosal protein content of the ileum. These results suggest that long-term intra-duodenal arginine administration may not have observable benefits on intestinal morphology or inflammatory response in rats with intestinal ischemia and reperfusion injury. Therefore, the necessity of long-term arginine supplementation for patients with intestinal ischemia and reperfusion injury remains questionable and requires further investigation.

Effect of Oral Supplementation with Branched-chain Amino Acid (BCAA) during Radiotherapy in Patients with Hepatocellular Carcinoma: A Double-Blind Randomized Study

PurposeThe present study evaluated whether oral supplementation with a branched-chain amino acid (BCAA) improves the biochemical and amino acid profiles of liver tumor patients undergoing radiotherapy.Materials and MethodsPatients were randomly assigned to one of 2 groups: a group given oral supplementation with BCAA granules (LIVACT granules; Samil Pharm Co., Korea, each granule containing L-isoleucine 952 mg, L-leucine 1,904 mg, and L-valine 1,144 mg) during radiotherapy, or a placebo group. Physical and biochemical examinations and measurements, including subjective symptoms, Child-Pugh class, body mass index, plasma albumin concentration, and plasma amino acid profiles were monitored.ResultsFifty were enrolled between November 2005 and November 2006. We also analyzed data from 37 hepatocellular carcinoma (HCC) patients in order to evaluate a more homogenous group. The two groups of patients were comparable in terms of age, gender, Child-Pugh score, and underlying hepatitis virus type. Serum albumin, total protein, liver enzymes, and cholesterol showed a tendency to increase in the BCAA group. In this group, the percentage of cases that reverted to normal serum albumin levels between 3 and 10 weeks after administration of BCAA was significantly higher (41.18%) than in the placebo group (p=0.043).ConclusionOral supplementation with a BCAA preparation seems to help HCC patients undergoing radiotherapy by increasing the BCAA concentration.

Plasma amino acid profile is altered by visceral fat accumulation and is a predictor of visceral obesity in humans

Abstract Background: The plasma amino acid profile can be a useful indicator in clinical settings because it changes in response to various metabolic alternations. However, the association between the plasma amino acid profile and body fat accumulation has not been evaluated in humans. Objective: This study aimed to relate plasma amino acids to visceral fat accumulation in humans because excess visceral fat raises the odds ratio of developing metabolic syndrome. Design: A total of 1,449 subjects (985 males and 464 females) who had undergone a comprehensive health screening were enrolled in this study. The visceral fat area (VFA) was determined in each subject using CT imaging. Subjects were then divided into two groups according to VFA: high-VFA (&8805;100 cm2, n=867) and low-VFA (<100 cm2, n=582). The plasma amino acid profile was analyzed together with other metabolic valuables and then compared between the two groups using uni- and multivariate analyses. Results: As the degree of visceral fat accumulation increased, plasma concentrations of several amino acids changed significantly. Glu, Val, Leu, Ile, Tyr, Ala, Phe, Pro, Lys, Orn, Trp, Met, His and alpha-aminobutyric acid (ABA) levels were significantly higher in the high-VFA group compared to the low-VFA group, whereas the levels of Gly, Ser, Gln and Asn were significantly lower. To evaluate the potential of using amino acids as an indicator of VFA, a discriminant analysis was conducted with the multivariate logistic regression analysis "AminoIndex", and the ROC curve was calculated. The resulting "AminoIndex" exhibited an area under the ROC curve of 0.81 (95% confidence interval; 0.78 to 0.83), with higher sensitivity and specificity by 80% and 65%, respectively. Conclusions: The plasma amino acid profile changes depending on visceral fat content and can be used as a marker for diagnosing elevated visceral obesity in humans.

Potential of Plasma Amino Acid Profiles for Use as Novel Diagnostic Marker for Prostate Cancer

Potential of Plasma Amino Acid Profiles for Use as Novel Diagnostic Marker for Prostate Cancer

Possibility of multivariate function composed of plasma amino acid profiles as a novel screening index for non-small cell lung cancer: a case control study

BackgroundThe amino-acid balance in cancer patients often differs from that in healthy individuals, because of metabolic changes. This study investigated the use of plasma amino-acid profiles as a novel marker for screening non-small-cell lung cancer (NSCLC) patients.MethodsThe amino-acid concentrations in venous blood samples from pre-treatment NSCLC patients (n = 141), and age-matched, gender-matched, and smoking status-matched controls (n = 423), were measured using liquid chromatography and mass spectrometry. The resultant study data set was subjected to multiple logistic regression analysis to identify amino acids related with NSCLC and construct the criteria for discriminating NSCLC patients from controls. A test data set derived from 162 patients and 3,917 controls was used to validate the stability of the constructed criteria.ResultsThe plasma amino-acid profiles significantly differed between the NSCLC patients and the controls. The obtained model (including alanine, valine, isoleucine, histidine, tryptophan and ornithine concentrations) performed well, with an area under the curve of the receiver-operator characteristic curve (ROC_AUC) of >0.8, and allowed NSCLC patients and controls to be discriminated regardless of disease stage or histological type.ConclusionsThis study shows that plasma amino acid profiling will be a potential screening tool for NSCLC.

Effect of corn particle size and soybean meal treatment on performance of finishing beef steers fed corn-silage-based diets

In the first experiment, 39 medium-frame beef steers (456 ± 41 kg) were used in a 2 × 2 factorial arrangement of treatments to evaluate the effect of different feeding strategies to maximize energy and protein deposition on finishing performance and plasma amino acid profile of beef steers fed corn silage ad libitum for 99 d. To achieve this goal, steers were individually supplemented with either 6.6 kg DM d-1 of cracked corn (CC) or ground corn (GC) in combination with 540 g DM d-1 of either solvent extracted (SS) or lignosulfonate-treated soybean meal (Soypass® SP). Dry matter intake, average daily gain and feed to gain ratio were not affected by treatments or by their interaction (P > 0.10). When compared with SS, SP tended to increase (P = 0.07) grade fat (1.3 and 2.2 ± 0.5 mm, respectively). The CC diets reduced the plasma concentration of branched-chained amino acids (P = 0.03) and leucine (P = 0.01), and tended to decrease that of isoleucine (P = 0.06) compared with the GC diets. No effect of diet was observed on plasma urea-N concentration. In the second experiment, four steers were used in a 4 × 4 Latin square design to evaluate digestibility and N balance of the diets used in exp. 1. Reducing particle size of corn increased apparent digestibility of starch (P = 0.01) and tended to reduce apparent digestibility of NDF (P = 0.07). In conclusion, formulating diets with ground or cracked corn in combination with solvent extracted or lignosulfonate-treated soybean meal does not appear to influence steer performance or digestion parameters.

Effects of feeding a ruminally protected lysine product, with or without isoleucine, valine and histidine, to lactating dairy cows on their productive performance and plasma amino acid profiles

The literature on post-ruminal lysine supplementation to diets of lactating dairy cows shows generally small negative responses to supplemental intestinally absorbable lysine, and our recent metabolic modeling of California dairy rations predicted other amino acid (AA) that could become co-limiting if supplies of intestinally absorbable lysine were met. The objectives of this study were to estimate the rumen escape potential of a ruminally protected (RP) lysine (RPL) product, and an RPL product also containing isoleucine, valine and histidine (RPAA), to determine effects of feeding these products on performance and plasma AA profiles of high producing dairy cows. Three pens of about 310 multiparous early lactation cows were used in a 3 × 3 Latin square design with 28 day experimental periods in which the basal total mixed ration (TMR) was the same for all groups except for the RP products which were added to the treatment pens at a level designed to deliver an equal amount of intestinally absorbable l-lysine to both RP groups. However rumen stability was slightly higher for the RPL versus the RPAA, and the RPL was calculated to deliver ∼13.2 g/d of intestinally absorbable lysine and the RPAA calculated to deliver ∼10.6, 5.4, 2.2 and 1.6 g/d of intestinally absorbable lysine, isoleucine, histidine and valine respectively. Only milk protein proportion was increased when RPL was fed. However, replacement of the RPL with the RPAA increased milk and milk lactose yields, while milk protein and energy outputs tended to increase. Plasma levels of both non-essential and essential AA, including lysine, were not impacted by feeding the RPL or RPAA. Overall, feeding the RPL alone was judged to cause a generally reduced productive performance, which could be interpreted to suggest that lysine was not supplied in sufficient quantity or that it was not required. Feeding the RPAA versus the RPL increased productive performance of the cows overall, which could support an overall hypothesis that lysine alone resulted in an imbalance and/or deficiency of isoleucine, histidine and/or valine which was alleviated by their supplementation. Overall treatment differences, regardless of their statistical significance, were small and of very limited practical application. Nevertheless, feeding a complex of RPAA was beneficial beyond supplementation of RP lysine alone, but more research on AA imbalances will be required in order to determine effects of supplementation of RP amino acids.

Associations between amino acids and bone mineral density in men with idiopathic osteoporosis

Idiopathic osteoporosis in middle-aged men is characterized by low-level bone formation. Inhibited anabolism may be involved in the pathogenesis of the disease and amino acids may be of importance. In the present study fasting amino acid profiles in plasma and erythrocytes were determined in 22 male idiopathic osteoporosis (MIO) patients and in 20 age-matched healthy men and associated with bone mineral density, bone histomorphometry and hormones. The osteoporotic patients had normal plasma essential amino acids but increased non-essential amino acids ( p = 0.001), particularly glutamine and glycine. The ratio essential/non-essential amino acids, an index of protein nutritional status, was decreased in the MIO patients (0.59 (0.04) μmol/l, mean (SD)), compared to controls (0.66 (0.05), p = 0.001). In the MIO patients, the ratio essential/non-essential plasma amino acids ( r = 0.60, p = 0.003) was positively correlated with lumbar spine bone mineral density. The erythrocyte amino acids represent a large proportion of the free amino acids in blood. A novel finding was the lower levels of erythrocyte tryptophan in MIO (12 (2) μmol/l) compared to controls (16 (3), p = 0.001) and decreased erythrocyte/plasma ratio (0.28 (0.07) vs. 0.33, (0.06), p < 0.01), suggesting an altered amino acid transport of tryptophan between plasma and erythrocytes. In the combined group of MIO and control men ( n = 42), bone mineral density was positively correlated with erythrocyte tryptophan in both the lumbar spine ( r = 0.45, p = 0.003) and femoral neck ( r = 0.56, p < 0.001). The bone histomorphometric variables wall thickness, trabecular thickness and mineral apposition rate were all positively associated with erythrocyte tryptophan levels in the MIO patients. In the combined group of MIO and controls, a multiple regression analysis showed that erythrocyte tryptophan could explain 22% of the variation of lumbar spine and 30% of the variation in femoral neck bone mineral density. We conclude that men with idiopathic osteoporosis have changes in free amino acid profiles which indicate their altered utilization. The correlations between tryptophan and bone mineral density and bone histomorphometry suggest a link between tryptophan and osteoblast function which may be important for bone health.

Maternal isovaleric acidemia: Observation of distinctive changes in plasma amino acids and carnitine profiles during pregnancy

Background Tandem mass spectrometry based newborn screening programs (NBS) allow early diagnosis and treatment for a number of inborn metabolic disorders. Despite the improved prognosis of affected individuals, the knowledge regarding the potential risks of childbearing in many of these conditions remains limited. Newborns with isovaleric acidemia (IVA) have been diagnosed by NBS and most of them can thrive and develop normally. Many affected individuals will therefore reach childbearing age in the near future. The information about maternal IVA, however, is quite limited. Case report Close observation of plasma amino acid, carnitine, and acylcarnitine profiles was performed in a patient with IVA that completed uneventful pregnancy. Plasma isovalerylcarnitine level was drastically decreased from the second trimester and free carnitine was inversely increased, suggesting reduced production of isovaleryl-CoA. This decrease of isovaleryl-CoA production was likely due to reduced leucine metabolism, secondary to the enhanced fetal anabolism associated with the rapid fetal growth of the second and the third trimesters. A decrease in maternal essential amino acids, including leucine was observed during the second and the third trimesters. Conclusion This observation revealed distinctive metabolic profiles during pregnancy in a patient with IVA and supports close laboratory monitoring and diet management for successful pregnancy.

Chemometric strategies to assess metabonomic imprinting of food habits in epidemiological studies

Application of metabonomics to nutritional sciences, also termed as nutrimetabonomics, offers the possibility to measure metabolic responses associated with the consumption of specific nutrients and foods. As dietary differences generally only lead to subtle metabolic changes, measuring diet associated metabolic phenotypes is a challenge, and also an opportunity to develop and test new chemometric strategies that can highlight metabolic information in relation to different dietary habits. While multivariate statistical techniques have long been used to analyse dietary data from diet records and questionnaires, to date no attempt has been made to link dietary patterns with metabolic profiles. Using a three-step strategy, it was possible to merge 1H NMR plasma metabolic profile data with specific dietary patterns as assessed by Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA). Five dietary patterns (energy intake, plant versus animal based diet, “traditional diet” versus sugar-rich diet, “traditional” versus “modern” diets, and consumption of skim versus whole dairy products) were found by applying PCA to the food frequency questionnaire data which explained 50% of the variation. Metabolic phenotypes associated with these dietary patterns were obtained by PLS-DA and were mainly based on differences in lipids and amino acid profiles in plasma. This new approach to assess relationships between dietary intake and metabolic profiling data will allow greater steps to be made in merging nutritional epidemiology with metabonomics.

Abstract 4632: Probability of plasma amino acid concentration and its profile as a novel diagnostic marker for prostate cancer

Abstract Introduction. Although there is no doubt on a plausible significance of prostate-specific antigen (PSA) on prostate cancer (PCa) diagnosis and managements, PSA screening for cancer has several problems especially on (1) specificity to discriminate cancers from benign lesions such as hypertrophy or inflammation, and (2) sensitivity to some cancers which PSA production is low or missing. Under the present circumstances, combination of other biomarkers with PSA is a way to overcome these problems. On the other hand, plasma amino acid-concentration reflects metabolic status of the body. Although maintained in healthy humans, it is known to change in various pathologic conditions including liver dysfunction and cancers, and therefore one could speculate that the profile of the change could be a promising biomarker (“AminoIndex”) of various cancers. Additionally, recent advances in technologies enable us to easily evaluate plasma amino acid profiles of a great number of samples. In this study, the potential of plasma amino acid profiling for prostate cancer detection was investigated. Subjects and Methods. Plasma samples were collected from Japanese prostate cancer patients those were consulted to Kanagawa Cancer Center Hospital and Yokohama Municipal Citizens Hospital and finally diagnosed by histopathological examination of biopsy specimens. Those of Japanese healthy controls were collected from subjects who were undergone comprehensive medical examination at Mitsui Memorial Hospital. Plasma amino acid-concentrations were measured by LC-MS, and compared between PCa patients and healthy controls. A multivariate logistic regression function was applied to obtain the index to discriminate PCa patients from controls using changes of plasma amino acid-concentrations. Results. Plasma concentrations of several amino acids changed significantly in PCa patients compared to control subjects. In particular, plasma levels of proline, alanine, and asparagine were increased while those of valine, and tryptophan were decreased in PCa patients significantly. The predicted amino acid profile index (“AminoIndex”) composed with these significantly changed amino acids showed high discrimination performance between PCa patients and healthy controls with more than 70% of area under ROC curve. The obtained index discriminated both patients of poorly differentiated cancer and the early stage cancer from control, and was independent of both age and serum PSA level. Conclusion and Perspectives. In this study, we demonstrated that plasma amino acid profile was altered in prostate cancer patients and the calculated “AminoIndex” could be a novel promising tool for detection of prostate cancer. PCa screening by the “AminoIndex” in conjunction with PSA could be a promising way to decrease both false positive and false negative cases. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4632.

Abstract 4633: A novel screening marker for breast cancer composed of plasma free amino acid concentrations “AminoIndex”

Abstract Introduction Amino acids balance is changed in patients of various diseases due to metabolic transition while it is maintained in healthy human. For example, it is known to change in liver dysfunction, renal failure, and cancers. Therefore, it is expected that the detection of metabolic transition using amino acid profiles is a promising screening marker of various cancers. We previously showed significant changes of plasma amino acid profiles and discriminating functions using plasma amino acid concentrations “AminoIndex” in various cancer patients including breast cancer. In this study, further possibilities of “AminoIndex” for breast cancer were investigated by case-control study from multiple medical facilities. Subjects and Methods Plasma samples were collected from Japanese breast cancer patients those were hospitalized in three hospitals and finally diagnosed before any medical treatment (N=295). Those of controls were also collected from subjects who were undergone comprehensive medical examination at two hospitals (N=2,147). Plasma amino acid concentrations were measured by LC-MS. Among them, 90 patients (30 from each hospital) in chronological order and 450 age-matched control subjects were chosen as training data set. And the rest (205 patients and 1,697 controls, respectively) were used as test data set to valid the inferred “AminoIndex”. Using training data set, plasma amino acid concentration were compared and then “AminoIndex”, multivariate logistic regression function composed of plasma amino acid concentrations, was inferred to discriminate breast cancer from control subjects. Results Plasma concentrations of several amino acids were significantly changed in breast cancer patients compared to control subjects. Predicted “AminoIndex” for breast cancer was resulted the multivariate logistic function composed with six amino acids. To evaluate the performance of the index predicted, the ROC curve for each predictive score was calculated, and this gave an AUC of ROC of 0.764 using the study data. Then, validation of predicted “AminoIndex” was performed using test data set, resulting almost same diagnostic performance. Furthermore, predicted “AminoIndex” showed notably features; the index could discriminate breast cancer patients almost equally in any stages, and the index showed not only higher discrimination performance than those of existing tumor markers but also distributed independently of the levels of various tumor markers. Therefore, predicted “AminoIndex” would be suitable for screening and early detection of breast cancer patients. Conclusion and Perspectives In this study, we demonstrated that change of plasma amino acid profile would be an indicator of breast cancer and a helpful tool for early detection of breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4633.

Effect of food form on postprandial plasma amino acid profiles in older adults

Purpose and MethodsTo assess the effect of food form on the postprandial (PP) plasma amino acid (AA) profile, 10 healthy older adults (5 men and 5 women, age 72 ± 2 y, BMI 26.0 ± 0.9 kg/m2) consumed energy and macronutrient matched test meals (~25% of subject's daily energy need; ~54% CHO, 21% Pro; 25% Fat) in beverage and solid form on separate days. Blood samples were taken during fasting (baseline) and throughout the 4‐hour PP period and plasma AA profiles (pmol/uL) were assessed using high performance liquid chromatography.ResultsThe consumption of each test meal led to an increase in total, branched chain (BCAA), essential (EAA), and non‐essential (NEAA) AA contents over the 4‐h period (time effect; p&lt;0.05). The beverage stimulated a greater increase in total, EAA and NEAA contents, but not BAA content, vs. the solid (effect of food form; p&lt;0.05). The beverage elicited higher plasma AA levels starting at 15 min PP which was maintained for the rest of the 4‐h period. The beverage also resulted in a greater total plasma AA 4‐h area under the curve (p&lt;0.05).ConclusionOlder adults can achieve higher plasma amino acid contents when a protein‐containing food is ingested in beverage form. Future research to explore the utility of this higher amino acid substrate availability on anabolic processes is needed.Support: NIH R01 AG021911, The Solae Company®, Purdue Ingest Behav Res Ctr and Bilsland Fellowship

P8 Mutagen sensitivity and p53 in suprabasal layers of tumor-distant oral mucosa in patients with oral squamous cell carcinoma

the rest were used as test data set to valid the predicted “AminoIndex”. Results: Plasma concentrations of several amino acids were significantly changed in breast cancer patients compared to control subjects in study data set. Finally, “AminoIndex” for breast cancer composed with six amino acids (Gln, Ala, ABA, Trp, Orn, and Arg) was predicted. To evaluate the performance, the ROC curve was calculated, and this gave an AUC of ROC of 0.832 using the study data. Validation of predicted “AminoIndex” using test data set resulted same discriminating performance (AUC of ROC of 0.822), suggesting the robustness of the predicted classifier. Furthermore, predicted AminoIndex showed notably features. 1. The index could discriminate breast cancer patients in early stages. 2. The index showed higher discrimination performance than those of existing tumor markers especially in stages 0, I, and II patients. 3. The index could equally discriminate breast cancer patients of any histological types. Therefore, predicted “AminoIndex” would be suitable for screening and early detection of breast cancer patients. Conclusion and Perspectives: In this study, we demonstrated that change of plasma amino acid profile would be a helpful tool for early detection of breast cancer patients. “AminoIndex” would be useful to concentrate and inspire the candidates for further survey such as mammography. To evaluate the efficacy of this method, cohort studies are ongoing.

Lifestyle Modification in Metabolic Syndrome and Associated Changes in Plasma Amino Acid Profiles

Although lifestyle modification is the key treatment of metabolic syndrome (MetS), clinical data on the dynamical relationship between metabolic state and MetS has been limited. This study investigated the mutual correlations between demographic and biochemical variables, and the metabolic state based on the plasma amino acid (AA) concentrations, during a lifestyle modification for MetS. Japanese subjects, consisting of 54 patients with MetS [MetS(+)] and 35 persons without MetS [MetS(-)] were included in the study. Before a lifestyle modification program, the levels of glutamate metabolism-related AA (Glu-mAA), aromatic AA metabolism-related AA (Aromatic-mAA) and alanine metabolism-related AA (Ala-mAA) were significantly higher, while those of glycine-serine-threonine metabolism-related AA (Gly-Ser-Thr-mAA) were significantly lower compared to those in MetS(-). After a lifestyle modification, significant reductions (P<0.05) in the BMI (-1.4 kg/m(2)), mean blood pressure (-7.9 mmHg), hemoglobin A(1c) (-0.4%), and triglycerides (-30.6 mg/dl) were observed, and significant differences in the plasma AA levels between MetS(+) and MetS(-) were resolved. In addition, the diagnostic items of MetS were positively correlated with the levels of Glu-mAA, Ala-mAA, branched chain AA (BCAA)-mAA, Aromatic-mAA, and negatively correlated with the levels of Gly-Ser-Thr-mAA. As MetS subsided, the abnormality of mean plasma AA levels of the MetS(+) group returned to similar values as those in the MetS(-) group, suggesting a novel viewpoint regarding the metabolic mechanism of lifestyle modification.

Plasma Amino Acid Profile in Horses following a Weighted Exercise Test

Plasma Amino Acid Profile in Horses following a Weighted Exercise Test

Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men

BackgroundIt has been reported that the blunted muscle protein synthetic response to food intake in the elderly can be normalized by increasing the leucine content of a meal. Objective:The objective was to assess the effect of 3 mo of leucine supplementation on muscle mass and strength in healthy elderly men. Design:Thirty healthy elderly men with a mean (±SEM) age of 71 ± 4 y and body mass index (BMI; in kg/m2) of 26.1 ± 0.5 were randomly assigned to either a placebo-supplemented (n = 15) or leucine-supplemented (n = 15) group. Leucine or placebo (2.5 g) was administered with each main meal during a 3-mo intervention period. Whole-body insulin sensitivity, muscle strength (one-repetition maximum), muscle mass (measured by computed tomography and dual-energy X-ray absorptiometry), myosin heavy chain isoform distribution, and plasma amino acid and lipid profiles were assessed before, during, and/or after the intervention period. Results:No changes in skeletal muscle mass or strength were observed over time in either the leucine- or placebo-supplemented group. No improvements in indexes of whole-body insulin sensitivity (oral glucose insulin sensitivity index and the homeostasis model assessment of insulin resistance), blood glycated hemoglobin content, or the plasma lipid profile were observed. Conclusion:Long-term leucine supplementation (7.5 g/d) does not augment skeletal muscle mass or strength and does not improve glycemic control or the blood lipid profile in healthy elderly men. This trial was registered at clinicaltrials.gov as NCT00807508.