Serum Sialic Acid Levels Research Articles

The diagnostic value of serum sialic acid for glioma

Objective To discuss the diagnostic value of serum sialic acid for glioma. Methods A retrospective study was conducted. The levels of sialic acid in serum samples of 95 glioma patients, 175 patients with brain benign tumor and 400 normal persons from October 2014 to March 2015 were detected by automatic biochemistry analyzer using enzymic method. The SNK-q test and analysis of variance were used to compare the difference of the groups. By making receiver operating characteristic (ROC) curve, the cut-off value, sensitivity, specificity, positive predictive value and negative predictive value were calculated to assess the diagnostic value of serum salivary acid. Then the cut-off value was validated by using the serums of 30 glioma patients and 30 normal persons who were out-patients and healthy controls. Results The levels of serum sialic acid in patients with gliomas, patients with brain benign tumor and healthy individuals were (0.66±0.14 ) g/L, (0.61±0.09 )g/L, (0.54±0.07 )g/L. The serum salivary acid of glioma patients were higher than brain benign tumor patients (q=6.74, P 0.05) among the glioma patients of different grades (8 of gradeⅠ, 32 of gradeⅡ, 24 of grade Ⅲ, 31 of grade Ⅳ). There was no significant difference between the low grade patients (grade Ⅰand Ⅱ) and the high grade patients (grade Ⅲ and Ⅳ) (t=0.55, P>0.05), but the level of serum sialic acid of high grade group had an increasing trend than the low grade group. The area under the ROC curves was 0.79. The cut-off value of serum salivary acid for diagnosing glioma was 0.61 g/L. The sensitivity was 67.74%, and the specificity was 80.60%. The positive predictive value was 44.68%, and the negative predictive value was 90.76%. Then the cut-off value was used as a diagnostic criteria, and the detected results of 30 glioma patients and 30 normal persons showed that the sensitivity was 63.30% and the specificity was 83.30%. Conclusions The serum sialic acid has good specificity and negative predictive value for diagnosing glioma. It may be a valuable diagnostic marker.(Chin J Lab Med, 2016, 39: 201-204) Key words: Glioma; Sialic acids; Diagnostic techniques and procedures; Sensitivity and specificity

Study on correlation between level of serum sialic acid and diabetic macular edema in patients with type 2 diabetic

Study on correlation between level of serum sialic acid and diabetic macular edema in patients with type 2 diabetic

Evaluation of some tumor markers, acute phase proteins, sialic acid and lipid bound sialic acid before and after chemotherapy in stomach cancer

Objective:  It was aimed to compare the some tumor markers, acute phase proteins, sialic acid and lipid bound sialic acid levels in patients with stomach cancer before and after chemotherapy to the healthy controls. Material and Methods:  Forty-eight patients with stomach adenocarcinoma and 20 healthy controls, totally 68 subjects were used. Blood samples were taken from all patients before and after chemotherapy and controls to analyse the levels of tumor markers (CA 125, CA 15-3, CA 19-9, CEA), acute phase proteins (CRP and fibrinogen) and SA (sialic acid), LSA (lipid bound sialic acid). Results:  Before chemotherapy the serum levels of CA 125, CA 15-3, CA 19-9, CEA SA, LSA, CRP and fibrinogen (107.30 U/ml, 65.74 U/ml, 295.86 U/ml, 108.57 ng/ml, 199.60 mg/dl, 41.89 mg/dl, 86.03 mg/l and 469.42 mg/dl ) were higher than after chemotherapy group (36.46 U/ml, 34.00 U/ml, 100.18 U/ml, 20.20 ng/ml, 87.67 mg/dl, 31.06 mg/dl, 57.04 mg/l and 379.04 mg/dl) and the controls (8.64 U/ml, 21.65 U/ml, 21.52 U/ml, 2.77 ng/ml, 73.75 mg/dl, 27.47 mg/dl, 2.37 mg/l, 303.5 mg/dl). Conclusion:  The serum levels of SA and LSA may be considered the indicators of poor/good prognosis of stomach cancer. CRP and fibrinogen are suggested as available biomarkers for diagnosis and prognosis in patients with stomach cancer.

Serum Sialic Acid Level Is Significantly Associated with Nonalcoholic Fatty Liver Disease in a Nonobese Chinese Population: A Cross-Sectional Study.

Background/Aim. To investigate the association between serum sialic acid (SA) levels and nonalcoholic fatty liver disease (NAFLD) in a nonobese Chinese population. Methods. A cross-sectional study was performed among the 5916 adults who took their annual health examinations at International Health Care Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, from December 2013 to November 2014. Results. A total of 693 (11.71%) subjects fulfilled the diagnostic criteria of NAFLD, and NAFLD patients had significantly higher serum SA levels than controls (P < 0.001). The prevalence of NAFLD was positively associated with serum SA levels (P for trend <0.001). Serum sialic acid levels are significantly associated with features of metabolic syndrome (Ps < 0.01). Multivariate logistic regression analysis showed that serum SA level was significantly associated with risk for NAFLD (odds ratio: 1.018, 95%; confidence interval: 1.007–1.030; P = 0.002). Conclusions. Our results suggest for the first time that NAFLD patients had higher serum SA level than controls, and increased serum SA level is significantly associated with risk for NAFLD in a large nonobese Chinese population.

The clinical value of serum sialic acid and lactadherin in the prognosis evaluation of atherosclerotic heart disease

Objective To discuss the effect and clinical value of serum sialic acid (SA)and lactadherin(MFG-E8)in the coronary atherosclerotic heart disease(CHD). Methods Selected 295 patients who visited to Wuhan University Renmin's Hospital cardiovascular medicine (from January to June, 2014), and then according to the results of coronary angiography divide the subjects into control group(n=78, the result of coronary angiography completely normal)and coronary heart disease group(n=217, the results of coronary angiography showed that one major coronary stenosis was more than 30%). Detected their serum level of lipid, SA, MFG-E8, hs-CRP index. At last, analyze the differences of SA and MFG-E8 between these groups, and the correlation with the severity of coronary stenosis (symbolize with Gensini score), use the binary logistic regression analysis to research the relationship among the serum level of SA, MFG-E8 and the risk of CHD. Results Compared with the control group, the patients with CHD have a higher level of serum SA and a lower level of MFG-E8 (U=4 402.5, 2 736.0 respectively, P<0.001); the AMI group has a higher level of serum SA than the StA and UA groups (U=1 329.0, 957.5 respectively, P<0.001); the AMI group has a lower level of serum MFG-E8 than the StA groups (U=1517.0, P<0.001). The spearman correlation analysis showed that the serum SA has a positively correlation with the level of TG, hs-CRP and Gensini score, and has a negatively correlated with the level of MFG-E8(r=0.214, 0.462, 0.378, -0.322 respectively, P<0.01); the MFG-E8 has a negatively correlated with the level of TG, hs-CRP and Gensini score (r=-0.18, -0.425, -0.564 respectively, P<0.01). Binary logistic regression analysis showed that there was a positive correlation between the serum SA and the risk of CHD (OD= 4.782, 5.319, 4.179 3.832, 3.648 respectively, P<0.001), and the was a negative correlation between the serum MFG-E8 and the risk of CHD (OD= 0.118, 0.112, 0.127, 0.135, 0.134 respectively, P<0.001). Conclusion With the serum SA rised and the MFG-E8 reduced, the risk of coronary heart disease was higher, combined detection these two indexes may be able to diagnose the CHD and assess the degree of stenosis and the risk of CHD.(Chin J Lab Med, 2015, 38: 746-750) Key words: Coronary disease; N-acetylneuraminic acid; Milk proteins; C-reactive protein; Risk factors

Evaluation of some tumor markers, acute phase proteins, sialic acid and lipid bound sialic acid before and after chemotherapy in stomach cancer

Objective: It was aimed to compare the some tumor markers, acute phase proteins, sialic acid and lipid bound sialic acid levels in patients with stomach cancer before and after chemotherapy to the healthy controls. Material and Methods: Forty-eight patients with stomach adenocarcinoma and 20 healthy controls, totally 68 subjects were used. Blood samples were taken from all patients before and after chemotherapy and controls to analyse the levels of tumor markers (CA 125, CA 15-3, CA 19-9, CEA), acute phase proteins (CRP and fibrinogen) and SA (sialic acid), LSA (lipid bound sialic acid). Results: Before chemotherapy the serum levels of CA 125, CA 15-3, CA 19-9, CEA SA, LSA, CRP and fibrinogen (107.30 U/ml, 65.74 U/ml, 295.86 U/ml, 108.57 ng/ml, 199.60 mg/dl, 41.89 mg/dl, 86.03 mg/l and 469.42 mg/dl ) were higher than after chemotherapy group (36.46 U/ml, 34.00 U/ml, 100.18 U/ml, 20.20 ng/ml, 87.67 mg/dl, 31.06 mg/dl, 57.04 mg/l and 379.04 mg/dl) and the controls (8.64 U/ml, 21.65 U/ml, 21.52 U/ml, 2.77 ng/ml, 73.75 mg/dl, 27.47 mg/dl, 2.37 mg/l, 303.5 mg/dl). Conclusion: The serum levels of SA and LSA may be considered the indicators of poor/good prognosis of stomach cancer. CRP and fibrinogen are suggested as available biomarkers for diagnosis and prognosis in patients with stomach cancer.

High fat diet-induced inflammation and oxidative stress are attenuated by N-acetylneuraminic acid in rats.

BackgroundSerum sialic acid levels are positively correlated with coronary artery disease and inflammation. Although sialic acid is a non-specific marker, it is considered sensitive likely due to its influence in sialylation of glycoprotein structures all over the body.ObjectivesWe hypothesized that dietary supplementation with N-acetylneuraminic acid (Neu5Ac), a type of sialic acid, will have profound effects on high fat diet- (HFD-) induced inflammation and oxidative stress in view of the widespread incorporation of sialic acid into glycoprotein structures in the body.MethodsHFD-fed rats with or without simvastatin or Neu5Ac (50 and 400 mg/kg/day) were followed up for 12 weeks. Lipid profiles, and markers of inflammation (C-reactive protein, interleukin-6, and tumor necrosis factor alpha), insulin resistance (serum insulin and adiponectin, oral glucose tolerance test and homeostatic model of insulin resistance) and oxidative stress (total antioxidant status and thiobarbituric acid reactive species) in the serum and liver were determined, while mRNA levels of hepatic antioxidant and inflammation genes were also quantified. Serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, urea, creatinine and uric acid were also assessed.ResultsHFD feeding caused hyperlipidemia and insulin resistance, and worsened liver and kidney functions. HFD feeding also potentiated inflammation and oxidative stress, partly through modulation of hepatic gene expression, while Neu5Ac especially at higher doses and simvastatin attenuated HFD-induced changes, although Neu5Ac showed better outcomes.ConclusionsBased on the present results, we surmised that Neu5Ac can prevent HFD-induced inflammation and oxidative stress, and may in fact be useful in the prevention of hyperlipidemia-associated inflammation and oxidative stress. However, the translational implications of these findings can only be determined after long-term effects are established. Hence, the use of Neu5Ac on obesity-related diseases requires additional attention.

Modulation of sialic acid levels among some organs during insulin resistance or hyperglycemic states.

Previous studies have suggested a possible connection between insulin resistance and chronic hyperglycemia with membrane sialic acid content. In this study, the effects of high (20% ad libitum) fructose and glucose feeding on the sialic acid levels of some organs were investigated in rats. The blood glucose levels of the high fructose- and glucose-fed rats were consistently and significantly (P < 0.05) higher than the normal control throughout the experiment. Free serum sialic acid and total hepatic sialic acid levels were elevated in the high fructose- and glucose-fed rats compared to normal control, but only the data for the high glucose-fed group were significantly (P < 0.05) different from the normal control. Conversely, a significant (P < 0.05) decrease in the pancreatic sialic acid level was observed in high glucose-fed group compared to normal control. Also, the high fructose-fed rats had lower, but insignificant (P > 0.05), pancreatic sialic acid level than the normal control. On the other hand, high fructose and glucose feeding did not significantly (P > 0.05) affect the sialic acid levels of the skeletal muscle and heart, though a tendency to increase the sialic acid level was evident in the heart. In the kidney, the sialic acid level was significantly (P < 0.05) increased in both high fructose- and glucose-fed groups. It was concluded that the liver and kidney tend to stimulate sialic acid synthesis, while the pancreas downregulate sialic acids synthesis and/or promote sialic acid release from glycoconjugates. Also, these organs may contribute to high-serum sialic acid level observed during diabetes.

Association between Serum Sialic Acid Levels and Nonalcoholic Fatty Liver Disease: A Cross-Sectional Study

Background: To assess the association between serum sialic acid (SA) levels and nonalcoholic fatty liver disease (NAFLD) in a Chinese population. Methods: A cross-sectional study was performed among 3,898 Chinese who took their annual health examination. Serum SA levels and other clinical and laboratory parameters were measured. Results: A total of 18.11% fulfilled the diagnostic criteria of NAFLD. NAFLD subjects with/without metabolic syndrome (MS) had significantly higher serum SA levels than those without NAFLD. Serum SA levels were significantly and positively correlated with components of MS (body mass index, systolic blood pressure, diastolic blood pressure, triglyceride and fasting plasma glucose) in the NAFLD group. Stepwise logistic regression analysis showed that SA levels were significantly associated with the risk factor for NAFLD. Serum SA levels were negatively correlated with the FIB-4 score, and lower serum SA levels were independent factors predicting advanced fibrosis in subjects with NAFLD. Conclusions: Our results showed a significant association between serum SA levels and NAFLD.

A study of circulating sialic acid levels in pregnancy

Background: The sialic acid level is significantly higher in full term cord firbrinogen than in controls and higher in premature than term samples and degree of hypersialation of fetal fibrinogen is a function of gestational age,prenatal diagnosis and confirmation of infantile sialic acid storage disease have been carried out by amniocentesis. Aims &amp; Objectives: To correlate the physiological stress occurring during different trimesters of pregnancy with circulating level of serum sialic acid. Methodology: In this study 30 blood samples were collected from healthy pregnant women in each trimester of pregnancy of age group between 18-35 years along with age and sex matched non pregnant control group. The blood samples was collected from all participants and analyzed for Serum sialic acid ,total protein, albumin and Blood sugar. Results: The mean concentration of serum sialic acid (Micmol/dl) in non pregnant control was estimated to be 119.1±4.68 as compared to 138.8± 4.57,155.76± 5.1, 171.18± 6.7 in first, second and third trimester of pregnancy respectively. Conclusion: The level of total sialic acid is found to be elevated as the pregnancy advances. This increase in maternal circulating serum TSA levels can be attributed to the immunological and metabolic adjustments that the pregnant women undergoes to bring about successful pregnancy.

Serum N-Glycans: A New Diagnostic Biomarker for Light Chain Multiple Myeloma.

The aim of this study was to evaluate the diagnostic and differential diagnostic power of serum N-glycans for light chain multiple myeloma (LCMM). A total of 167 cases of subjects, including 42 LCMM, 42 IgG myeloma, 41 IgA myeloma, and 42 healthy controls were recruited in this study. DNA sequencer-assisted fluorophore-assisted capillary electrophoresis (DSA-FACE) was applied to determine the quantitive abundance of serum N-glycans. The core fucosylated, bisecting and sialylated modifications were analyzed in serum of LCMM patients (n=20) and healthy controls (n=20) randomly selected from the same cohort by lectin blot. Moreover, serum sialic acid (SA) level was measured by enzymatic method. We found two N-glycan structures (NG1A2F, Peak3; NA2FB, Peak7) showed the optimum diagnostic efficacy with area under the ROC curve (AUC) 0.939 and 0.940 between LCMM and healthy control. The sensitivity and specificity of Peak3 were 88.1% and 92.9%, while Peak7 were 92.9% and 97.6%, respectively. The abundance of Peak3 could differentiate LCMM from IgG myeloma with AUC 0.899, sensitivity 100% and specificity 76.2%, and Peak7 could be used to differentiate LCMM from IgA myeloma with AUC 0.922, sensitivity 92.9% and specificity 82.9%. Serum SA level was significantly higher in patients with LCMM than that in healthy controls. Moreover, the decreased core fucosylation, bisecting and increased sialylation characters of serum glycoproteins were observed in patients with LCMM. We concluded that serum N-glycan could provide a simple, reliable and non-invasive biomarker for LCMM diagnosis and abnormal glycosylation might imply a new potential therapeutic target in LCMM.

Evaluation of serum sialic acid, fucose levels and their ratio in oral squamous cell carcinoma.

Background:Detection of cancer at the early stage is of utmost importance to decrease the morbidity and mortality of the disease. Apart from the conventional biopsy, minimally invasive methods like serum evaluation are used for screening large populations. Thus, this study aimed to estimate serum levels of sialic acid and fucose and their ratio in oral cancer patients and in healthy control group to evaluate their role in diagnosis.Materials and Methods:Serum samples were collected from 52 healthy controls (group I) and 52 squamous cell carcinoma patients (group II). Estimation of serum levels of sialic acid and fucose and their ratio was performed. This was correlated histopathologically with the grades of carcinoma. Statistical analysis was done by using analysis of variance (ANOVA) test and unpaired “t” test.Results:Results showed that serum levels of sialic acid and fucose were significantly higher in oral cancer patients compared to normal healthy controls (P < 0.001). The sialic acid to fucose ratio was significantly lower in cancer patients than in normal controls (P < 0.01). However, comparison with histological grading, habits, gender, and age group did not show any significant result.Conclusion:The mean serum sialic acid and fucose levels showed an increasing trend from controls to malignant group and their corresponding ratio showed decreasing trend from controls to malignant group. The ratio of sialic acid to fucose can be a useful diagnostic aid for oral cancer patients.

Sialic acid Levels in smokers and nonsmokers with malignant pleural effusion

Objective: The present study is designed to measure sialic acid in pleural effusion and in serum samples of patients to differentiate between malignant and nonmalignant diseases. Materials and Methods: The present study was conducted on 30 patients with malignant pleural effusion and 30 patients with nonmalignant pleural effusion. Pleural fluid and blood samples were taken at the time of admission, before starting any treatment. Sialic acid levels were estimated in serum and pleural fluid by Warren's Thiobarbituric Acid (TBA) method. Results: In the present study, serum sialic acid levels were higher in group II as compared to group I. In the present study, pleural fluid (PF) sialic acid levels and PF/serum(S) ratio was higher in malignant pleural effusion (though difference was not statistically significant). Smokers in group II had higher serum sialic acid as compared to group 1 ( P Conclusion: These findings indicate that determination of sialic acid levels in pleural fluid has diagnostic value as a cheap, simple, and reliable marker for malignant pleural effusion.

Relationship between Serum Sialic Acid and Hemostatic Markers in Patients with Type 2 Diabetes Mellitus.

Serum sialic acid (SA) is an acute phase response marker. Additionally, it is an independent risk factor for atherosclerotic disease and is higher in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to determine the association of SA with blood coagulation and fibrinolysis in T2DM patients. The levels of serum SA and blood coagulation and fibrinolysis markers were measured in patients with T2DM. The associations of SA with hemostatic markers and other variables were assessed. There were significant correlations between SA and fibrinogen, D-dimer, factor (F) IX, and platelet (PLT) that were independent of smoking, body mass index (BMI), waist-to-hip ratio, hemoglobin A(1c) (HbA1c), fasting plasma glucose (FPG), triglycerides (TG), total cholesterol (TC) to high-density lipoprotein cholesterol (HDL-C) ratio, and antithrombotic therapy history. Based on logistic regression analyses, the highest tertile groups of fibrinogen, D-dimer, F VIII, F IX, and PLT showed a significantly increased risk of high SA compared with the lowest tertiles after adjusting for age, gender, and antithrombotic therapy history. SA also significantly correlated with duration of diabetes, BMI, FPG, TG, low-density lipoprotein cholesterol (LDL-c), TC-to-HDL-C ratio, and albumin-to-creatinine ratio (ACR). Elevated serum SA levels are associated with increased coagulability and higher risk of thrombus formation in T2DM patients.

Protective Effect of Solanum muricatum on Tumor Metastasis by Regulating Inflammatory Mediators and Nuclear Factor-Kappa B Subunits

Metastasis is one of the hallmarks of malignant neoplasm or cancer, which is the leading cause of death in many cancer patients. A major challenge in cancer treatment is to find better ways to specifically target tumor metastases. In this study, the anti-metastatic potential of the methanol extract of Solanum muricatum (S. muricatum) was evaluated using B16F-10 melanoma cell-induced lung metastasis in C57BL/6 mice. Treatment with S. muricatum significantly inhibited the lung tumor nodule formation and reduced the lung collagen hydroxyproline, hexosamine, and uronic acid levels (p<0.01). Similarly, serum sialic acid and γ-glutamyl transpeptidase levels were also significantly inhibited after S. muricatum treatment. The levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, granulocyte monocyte colony-stimulating factor (GM-CSF), and IL-2 in serum were significantly regulated after treatment with S. muricatum. The serum nitric oxide level was also decreased significantly and was accompanied by a decrease in inducible nitric oxide synthase (iNOS) and cyclo- oxygenase (COX)-2 expressions after S. muricatum treatment. The present study reveals that S. muricatum treatment was able to alter the proinflammatory cytokine production as well as inhibit the activation and nuclear translocation of nuclear factor-κB (p65 and p50) subunits.

Desialylation Induces Apoptosis and Phagocytosis of Platelets in Patients with Prolonged Isolated Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation

Introduction:Prolonged isolated thrombocytopenia (PIT) represents a significant complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and is associated with an adverse patient prognosis and higher transplant-related mortality owing to a higher risk of infection events, severe (grades 3 to 4) acute graft-versus-host disease (GVHD) and chronic GVHD. PIT is defined as a peripheral platelet count less than 100×109/L without sustained anemia or leukopenia for more than 3 months after allo-HSCT (Zhang X, et al. Biol Blood Marrow Transplant, 2011). However, the underlying mechanisms remain unclear. Different kinds of functional glycoproteins are expressed on the platelet surface, with sialic acid residues at the end of their glycan. Desialylation of platelet glycoproteins has been found to be associated with accelerated platelet clearance in refrigerated platelets (Gerard Jansen AJ, et al. Blood 2012). Platelet-specific glycoprotein GPIbα,the functional subunit of the von Willebrand factor receptor, was the majorly desialylated glycoprotein; NEU1, one of the four human sialidases, was the enzyme that catalyzed GPIbα desialylation. However, few studies have focused on this mechanism in patients suffering PIT after allo-HSCT. In this study, we hypothesized that desialylation on platelet surfaces is associated with PIT after allo-HSCT. The mechanisms participating in this process may include GPIbα clustering, platelet apoptosis and phagocytosis by macrophages.Patients and methods:Blood samples were collected 90 days after allo-HSCT from 70 patients with PIT. Samples from post-transplantation patients who have normal platelet counts were taken as controls. Sialylation and desialylation were measured by detecting specific lectins via flow cytometry. Human sialidase expression was determined by immunofluorescence, flow cytometry and reverse transcription PCR. Platelet apoptosis markers were measured by flow cytometry, and macrophages stimulated from THP-1 cells were used in the phagocytosis assay.Results:We tested sialic acid residues and the desialylation markers, including β-galactose and β-N-Acetyl glucosamine, on the platelet surface, and found that platelets from PIT patients had significantly higher desialylation levels. Serum sialic acid levels were measured, and the results showed higher levels in PIT patients. Further, NEU1 was found to be over-expressed on the surface of platelets from PIT patients, and was found to be the enzyme that catalyzed the platelet surface desialylation. To further reveal the mechanism that lead to PIT, we proved that GPIbα was the desialylated glycoprotein on platelets from PIT patients. We found that GPIbα desialylation and clustering in PIT patients induced changes in the expression of Bcl-2 family protein, as a 2-fold increase in active Bax expression and a similar decrease in Bcl-XL expression were observed. Depolarization of the inner mitochondria membrane was augmented in desialylated platelets from PIT patients, indicating increased platelet apoptosis. Moreover, macrophages stimulated from the THP-1 cell line preferred to phagocytose desialylated platelets from PIT patients in vitro; this process could be blocked by the sialidase inhibitor, DANA. In the in vitrostudy, we found that dexamethasone led to a 32% decrease in phagocytosis, whereas oseltamivir, an antiviral medicine that can block sialidase from influenza virus, could also partially function on human sialidase and protect 43% of platelets from phagocytosis.In conclusion, our results demonstrate that desialylation played a role in the mechanism of prolonged isolated thrombocytopenia after allo-HSCT, most likely through platelet apoptosis induction and increased phagocytosis by macrophages in the peripheral circulation. Dexamethasone and oseltamivir could decrease platelet apoptosis and inhibit platelet phagocytosis in vitro, implying a novel potential method for treating PIT after allo-HSCT. DisclosuresNo relevant conflicts of interest to declare.

T.I.2: Therapeutic efforts in GNE myopathy

GNE myopathy (also known as HIBM or DMRV) is an autosomal recessive disease due to biallelic mutations in GNE , a gene encoding for a key enzyme in sialic acid biosynthesis. It is assumed that the presence of the mutated protein (or lack of its normal activity) and muscle hyposialylation contribute to the pathophysiology of the disease. Given the putative pathophysiology several therapy approaches are being tried: 1. Metabolic bypass with- a. oral supplementation of high dose sialic acid (both as extended release and regular capsules). 48weeks results of an ongoing trial in 46 patients show clinically meaningful effect in stabilizing upper extremities muscle strength associated with increased serum levels of sialic acid (H. Lau – this meeting). b. oral ManNAc (a precursor of sialic acid). Phase 1 trial has been concluded. c. IVG which contains high sialic acid showed modest effect and was abandoned. 2. Gene therapy- a. compassionate trial in a single patient used IV liposomal delivery of GNE coupled to CMV promoter. Proof of concept for mild increased sialylation was observed. b. viral-mediated gene therapy. A platform for human therapy trial has been developed based on AAV8 harboring the wild type human GNE and driven by MCK promoter. Single IV injection of this construct proved safe and resulted in human GNE expression in normal mice (Mitrani Rosenbaum – this meeting). Now that therapies are under investigation, it is critical that patients with GNE myopathy should be identified at the early stages of the disease. Disclosure: ZA is a consultant for Ultragenyx and Bioblast pharma.

G.O.27: Randomized controlled phase 2 study of GNE myopathy subjects treated with placebo, 6 g or 3 g doses of extended-release sialic acid (SA-ER) and an extension study at a higher 12 g dose of combination extended and immediate release sialic acid (SA)

SA-ER was investigated in a Phase 2 randomized, double-blind, placebo-controlled 48week study evaluating dose, PK and clinical efficacy. 47 subjects were originally enrolled and randomized to receive either placebo, 3g or 6g of SA-ER/day. After 24weeks, placebo patients crossed to either 3g or 6g dose/day for an additional 24weeks. After a variable extension period at 6g, all 46 continuing subjects and 13 newly enrolled naive subjects were treated with a 50:50 combination of SA-ER plus SA at a dose of12 g per day to assess whether a higher dose and serum SA level would have better efficacy. Study assessments included PK, muscle strength by hand-held dynamometry [(HHD) composites of upper extremity (UEC), lower extremity (LEC)], other clinical endpoints, patient reported outcomes (PRO) and safety. Muscle strength assessments by HHD at 24weeks showed that the UEC in the 6g group was significantly greater than placebo (+2.33kg, p =0.04). At 48weeks after placebo subjects crossed over, the combined 6g group was significantly superior than the combined 3g group (+3.44kg, p =0.0033) and the difference was larger in the predefined >200m baseline 6MWT walking group (+4.70kg, p ; p =0.087), mobility ( p =0.087) and UE scores ( p =0.096) in the combined 6g vs. the combined 3g group by ANCOVA. Clinical endpoints related to walking (e.g. 6 MWT) did not reveal significant changes. The impact of an increased dose of 12g in the 46 continuing and in 13 naive HIBM subjects will be presented. SA-ER appeared to be well tolerated with no serious adverse events observed at 3 or 6g/day. These data suggest that the SA-ER 6g dose is having a clinically meaningful effect stabilizing UEC muscle strength.

The association of total sialic acid and malondialdehyde levels with metabolic and anthropometric variables in obesity

Serum sialic acid levels are abnormally high in pathological states that exhibit tissue destruction, tissue proliferation or inflammation. We measured total serum sialic acid levels in 139 women and 125 men. Subjects were divided into quartiles according to their body mass index (BMI): Q1 (18–24.9 kg/m2), Q2 (25–29.9 kg/m2), Q3 (30–39.9 kg/m2) and Q4 (> 40 kg/m2). The patients in Q1 constituted the control group. Serum sialic acid levels of subjects in Q2, Q3 and Q4 were significantly higher than those in Q1. Higher BMI quartiles also were associated with higher levels of serum glucose, insulin, total cholesterol, LDL-cholesterol, triglycerides, high-sensitivity C-reactive protein, malondialdehyde levels, waist circumference, blood pressure and homeostasis model assessment of insulin resistance in both women and men. Lower BMI quartiles were associated with higher levels of serum HDL-cholesterol levels in both women and men. We found positive associations among serum sialic acid levels, BMI and oxidative stress. Serum sialic acid also is related to some conventional cardiovascular risk factors including elevated lipid profile, increased blood pressure, increased serum glucose and insulin levels, and insulin resistance in obese people.

Supplementation of fish oil augments efficacy and attenuates toxicity of 5-fluorouracil in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium-induced colon carcinogenesis.

5-Fluorouracil (5-FU) is used for the treatment of colorectal cancer, but has low therapeutic response rate and severe side effects. Recently, fish oil (FO) rich in n-3 polyunsaturated fatty acids has been preferred to chemosensitize tumor cells to anticancer drugs. Therefore, the current study is designed to evaluate chemotherapeutic efficacy and toxicity profile of 5-FU in combination with FO in 1,2-dimethylhydrazine dihydrochloride/dextran sulfate sodium (DMH/DSS)-induced colon cancer model. The therapeutic efficacy of 5-FU along with FO was analyzed through assessment of survival rate, tumor burden, volume, serum sialic acid levels, cytokeratin 19 (CK19) expression and index of cell proliferation such as cell cycle progression. Toxicological aspects were evaluated by standard functional and structural parameters related to spleen, gastrointestinal, liver and kidney. In the present study, 5-FU in combination with FO increased the survival rate in carcinogen-treated animals. Synergism of 5-FU and FO was also reflected in significant inhibition in tumor growth and serum sialic acid levels in DMH/DSS model. Moreover, the combination dosage significantly augmented the inhibition of cell cycle progression, as shown by CK19 expression. Additionally, FO ameliorated hematologic depression, gastrointestinal, hepatic and renal toxicity caused by 5-FU as substantiated by a marked improvement in structural and functional alterations of these organs. The supplementation of FO is potentially a promising option for increasing the therapeutic potential and mitigating the side effects of 5-FU.