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Chen Z, Wu G, Lin X, Huang X, Zhang S, Chen K, Liang Z, Zhu X. The Prognostic Value of Serum Sialic Acid in Patients with Nasopharyngeal Carcinoma: A Propensity Score Matching Study. Cancer Manag Res 2024; 16:215-224. [PMID: 38525372 PMCID: PMC10961078 DOI: 10.2147/cmar.s448238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 03/09/2024] [Indexed: 03/26/2024] Open
Abstract
Purpose Elevated serum sialic acid (SA) is one of the indicators of poor prognosis in various malignant tumors. This study intends to determine the relationship between serum SA levels and survival prognosis in nasopharyngeal carcinoma (NPC). Patients and Methods From 2014 to 2016, NPC patients with no distance metastasis undergoing intensity-modulated radiotherapy (IMRT) were retrospectively analyzed. The serum SA levels before initial treatment were measured, and an optimal cut-off level was determined by X-tile software. A propensity score matching (PSM) technique was applied to reduce intergroup differences between the low serum SA level group and the high serum SA level group. Chi-square tests were utilized for comparing intergroup differences, Kaplan-Meier approach was utilized for plotting survival curves, and univariate and multivariate Cox proportional hazards regression models were employed for analyzing prognostic factors. Results Overall, 293 NPC patients with no distance metastasis were included. The optimal cut-off level of serum SA was 65.10 mg/dl. The baseline levels after PSM were more balanced compared to those before PSM. Survival analysis showed that the locoregional relapse-free survival (LRRFS, p=0.010), distant metastasis-free survival (DMFS, p=0.014), progression-free survival (PFS, p=0.009), and overall survival (OS, p=0.015) survival curves of the low serum SA level group and high serum SA level group were statistically significant differences. Univariate analysis showed that American Joint Committee on Cancer (AJCC) stage, T stage, N stage, neoadjuvant chemotherapy (NC), and serum SA expression level were factors influencing the prognosis of NPC patients. Multivariate analysis showed that high serum SA expression level was related to worse PFS and OS in NPC patients with no distance metastasis. Conclusion High serum SA level (SA > 65.10 mg/dl) before treatment is associated to poor survival outcomes in NPC and is an independent adverse prognostic factor in NPC patients with no distance metastasis.
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Affiliation(s)
- Zetan Chen
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China
- Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China
| | - Gang Wu
- Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China
| | - Xiangying Lin
- Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China
| | - Xiaopeng Huang
- Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China
| | - Shuai Zhang
- Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan, 570311, People’s Republic of China
| | - Kaihua Chen
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China
| | - Zhongguo Liang
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China
| | - Xiaodong Zhu
- Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China
- Department of Oncology, Wuming Hospital of Guangxi Medical University, Nanning, Guangxi, 530199, People’s Republic of China
- Key Laboratory of Early Prevention and Treatment for Regional High-Incidence-Tumor, Guangxi Medical University, Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China
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Golden RK, Sutkus LT, Bauer LL, Donovan SM, Dilger RN. Determining the safety and efficacy of dietary supplementation with 3'-sialyllactose or 6'-sialyllactose on growth, tolerance, and brain sialic acid concentrations. Front Nutr 2023; 10:1278804. [PMID: 37927504 PMCID: PMC10620723 DOI: 10.3389/fnut.2023.1278804] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 09/26/2023] [Indexed: 11/07/2023] Open
Abstract
Sialylated oligosaccharides, including 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL), comprise a large portion of human milk and have been known to support development over the first year of life. While research has investigated the impact of early-life supplementation, longer-term supplementation remains relatively unexplored. Consequently, the following study assesses the impact of supplementation of either 3'-SL or 6'-SL on growth performance, tolerance, and brain sialic acid concentrations. Two-day-old piglets (n = 75) were randomly assigned to a commercial milk replacer ad libitum without or with 3'-SL or 6'-SL (added at 0.2673% on an as-is basis). Daily body weight and feed disappearance were recorded to assess growth performance and tolerance. Pigs were euthanized for sample collection on postnatal day 33 (n = 30) or 61 (n = 33), respectively. Across growth performance, clinical chemistry and hematology, histomorphology, and sialic acid quantification, dietary differences were largely unremarkable at either time-point. Overall, SA was well-tolerated both short-term and long-term.
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Affiliation(s)
- Rebecca K. Golden
- Neuroscience Program, University of Illinois, Urbana, IL, United States
| | - Loretta T. Sutkus
- Neuroscience Program, University of Illinois, Urbana, IL, United States
| | - Laura L. Bauer
- Department of Animal Sciences, University of Illinois, Urbana, IL, United States
| | - Sharon M. Donovan
- Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL, United States
- Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
| | - Ryan N. Dilger
- Neuroscience Program, University of Illinois, Urbana, IL, United States
- Department of Animal Sciences, University of Illinois, Urbana, IL, United States
- Division of Nutritional Sciences, University of Illinois, Urbana, IL, United States
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Bupp CR, Schwartz C, Wei B, Wirth MJ. Protein-induced conformational change in glycans decreases the resolution of glycoproteins in hydrophilic interaction liquid chromatography. J Sep Sci 2021; 44:1581-1591. [PMID: 33682335 DOI: 10.1002/jssc.202001242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 03/01/2021] [Accepted: 03/02/2021] [Indexed: 11/08/2022]
Abstract
An understanding of why hydrophilic interaction liquid chromatography gives a higher resolution for glycans than for glycoproteins would facilitate column improvements. Separations of the glycoforms of ribonuclease B compared to its released glycans were studied using a commercial hydrophilic interaction liquid chromatography column. The findings were used to devise a new hydrophilic interaction liquid chromatography column. For the commercial column, chromatograms and van Deemter plots showed that selectivity and efficiency are comparable factors in the higher resolution of the released glycans. The higher selectivity for the released glycans was associated with more water molecules displaced per added mannose. To investigate why, three-dimensional structures of the glycoprotein and the glycan were computed under chromatographic conditions. These showed that hydrogen bonding within the free glycan makes its topology more planar, which would increase contact with the bonded phase. The protein sterically blocks the hydrogen bonding. The more globular-shaped glycan of the glycoprotein suggests that a thicker bonded phase might improve selectivity. This was tested by making a column with a copolymer bonded phase. The results confirmed that selectivity is increased. The findings are possibly broadly relevant to glycoprotein analysis since the structural motif involved in internal hydrogen bonding is common to N-linked glycans of human glycoproteins.
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Affiliation(s)
- Charles R Bupp
- Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana, USA
| | - Cameron Schwartz
- Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana, USA
| | - Bingchuan Wei
- Genentech, Inc. One DNA Way, South San Francisco, California, USA
| | - Mary J Wirth
- Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana, USA
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Derruau S, Robinet J, Untereiner V, Piot O, Sockalingum GD, Lorimier S. Vibrational Spectroscopy Saliva Profiling as Biometric Tool for Disease Diagnostics: A Systematic Literature. Molecules 2020; 25:E4142. [PMID: 32927716 PMCID: PMC7570680 DOI: 10.3390/molecules25184142] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 09/05/2020] [Accepted: 09/05/2020] [Indexed: 02/07/2023] Open
Abstract
Saliva is a biofluid that can be considered as a "mirror" reflecting our body's health status. Vibrational spectroscopy, Raman and infrared, can provide a detailed salivary fingerprint that can be used for disease biomarker discovery. We propose a systematic literature review based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to evaluate the potential of vibrational spectroscopy to diagnose oral and general diseases using saliva as a biological specimen. Literature searches were recently conducted in May 2020 through MEDLINE-PubMed and Scopus databases, without date limitation. Finally, over a period of 10 years, 18 publications were included reporting on 10 diseases (three oral and seven general diseases), with very high diagnostic performance rates in terms of sensitivity, specificity, and accuracy. Thirteen articles were related to six different cancers of the following anatomical sites: mouth, nasopharynx, lung, esophagus, stomach, and breast. The other diseases investigated and included in this review were periodontitis, Sjögren's syndrome, diabetes, and myocardial infarction. Moreover, most articles focused on Raman spectroscopy (n = 16/18) and more specifically surface-enhanced Raman spectroscopy (n = 12/18). Interestingly, vibrational spectroscopy appears promising as a rapid, label-free, and non-invasive diagnostic salivary biometric tool. Furthermore, it could be adapted to investigate subclinical diseases-even if developmental studies are required.
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Affiliation(s)
- Stéphane Derruau
- Université de Reims Champagne-Ardenne, Département de Biologie Orale, UFR Odontologie, 2 rue du Général Koenig, 51100 Reims, France; (S.D.); (J.R.)
- Pôle de Médecine Bucco-dentaire, Centre Hospitalier Universitaire de Reims, 45 rue Cognacq-Jay, 51092 Reims, France
- Université de Reims Champagne-Ardenne, BioSpecT-EA7506, UFR de Pharmacie, 51 rue Cognacq-Jay, 51097 Reims, France; (O.P.); (G.D.S.)
| | - Julien Robinet
- Université de Reims Champagne-Ardenne, Département de Biologie Orale, UFR Odontologie, 2 rue du Général Koenig, 51100 Reims, France; (S.D.); (J.R.)
| | - Valérie Untereiner
- Université de Reims Champagne-Ardenne, PICT, 51 rue Cognacq-Jay, 51097 Reims, France;
| | - Olivier Piot
- Université de Reims Champagne-Ardenne, BioSpecT-EA7506, UFR de Pharmacie, 51 rue Cognacq-Jay, 51097 Reims, France; (O.P.); (G.D.S.)
- Université de Reims Champagne-Ardenne, PICT, 51 rue Cognacq-Jay, 51097 Reims, France;
| | - Ganesh D. Sockalingum
- Université de Reims Champagne-Ardenne, BioSpecT-EA7506, UFR de Pharmacie, 51 rue Cognacq-Jay, 51097 Reims, France; (O.P.); (G.D.S.)
| | - Sandrine Lorimier
- Université de Reims Champagne-Ardenne, Département de Biologie Orale, UFR Odontologie, 2 rue du Général Koenig, 51100 Reims, France; (S.D.); (J.R.)
- Pôle de Médecine Bucco-dentaire, Centre Hospitalier Universitaire de Reims, 45 rue Cognacq-Jay, 51092 Reims, France
- Université de Reims Champagne-Ardenne, GRESPI-EA4694, UFR Sciences Exactes et Naturelles, 51687 Reims, France
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Huang D, Gaul DA, Nan H, Kim J, Fernández FM. Deep Metabolomics of a High-Grade Serous Ovarian Cancer Triple-Knockout Mouse Model. J Proteome Res 2019; 18:3184-3194. [PMID: 31290664 DOI: 10.1021/acs.jproteome.9b00263] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
High-grade serous carcinoma (HGSC) is the most common and deadliest ovarian cancer (OC) type, accounting for 70-80% of OC deaths. This high mortality is largely due to late diagnosis. Early detection is thus crucial to reduce mortality, yet the tumor pathogenesis of HGSC remains poorly understood, making early detection exceedingly difficult. Faithfully and reliably representing the clinical nature of human HGSC, a recently developed triple-knockout (TKO) mouse model offers a unique opportunity to examine the entire disease spectrum of HGSC. Metabolic alterations were investigated by applying ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to serum samples collected from these mice at premalignant, early, and advanced stages of HGSC. This comprehensive analysis revealed a panel of 29 serum metabolites that distinguished mice with HGSC from controls and mice with uterine tumors with over 95% accuracy. Meanwhile, our panel could further distinguish early-stage HGSC from controls with 100% accuracy and from advanced-stage HGSC with over 90% accuracy. Important identified metabolites included phospholipids, sphingomyelins, sterols, N-acyltaurine, oligopeptides, bilirubin, 2(3)-hydroxysebacic acids, uridine, N-acetylneuraminic acid, and pyrazine derivatives. Overall, our study provides insights into dysregulated metabolism associated with HGSC development and progression, and serves as a useful guide toward early detection.
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Affiliation(s)
- Danning Huang
- School of Chemistry and Biochemistry , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States
| | - David A Gaul
- School of Chemistry and Biochemistry , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States
| | | | | | - Facundo M Fernández
- School of Chemistry and Biochemistry , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States
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Hernández-Cedillo A, García-Valdivieso MG, Hernández-Arteaga AC, Patiño-Marín N, Vértiz-Hernández ÁA, José-Yacamán M, Navarro-Contreras HR. Determination of sialic acid levels by using surface-enhanced Raman spectroscopy in periodontitis and gingivitis. Oral Dis 2019; 25:1627-1633. [PMID: 31177594 DOI: 10.1111/odi.13141] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 05/14/2019] [Accepted: 05/28/2019] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To compare the sialic acid (SA) levels in saliva among periodontitis-affected, gingivitis and control patients. METHODS The study involved 93 subjects. The participants were divided into three groups: (1) 30 subjects without periodontal disease (control group); (2) 30 subjects with gingivitis; and (3) 33 subjects with periodontitis. The oral parameters examined were as follows: (a) Simplified Oral Hygiene Index; (b) Calculus Index; (c) Gingival Index; (d) probing pocket depth; and (e) level of epithelial attachment. SA levels in saliva were measured by means of surface-enhanced Raman spectroscopy (SERS). This method has demonstrated the capacity to detect extremely low concentrations of molecules. The spectrum was calibrated using analytical reagent SA. RESULTS The obtained median values for SA concentrations were 5.98, 7.32, and 17.12 mg/dl for control, gingivitis, and periodontitis patients, respectively. CONCLUSIONS Our measurements by SERS corroborate that in periodontitis-affected patients, the SA concentration is larger than their concentrations in either control or gingivitis patients. This confirms previous reports and opens the possibility of using SERS as a diagnostic tool.
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Affiliation(s)
- Alondra Hernández-Cedillo
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luís Potosí, San Luis Potosí, México
| | - Ma Guadalupe García-Valdivieso
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luís Potosí, San Luis Potosí, México
| | - Aida Catalina Hernández-Arteaga
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luís Potosí, San Luis Potosí, México
| | - Nuria Patiño-Marín
- Facultad de Estomatología, Universidad Autónoma de San Luís Potosí, San Luis Potosí, México
| | | | - Miguel José-Yacamán
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luís Potosí, San Luis Potosí, México.,Department of Physics and Astronomy, University of Texas at San Antonio, San Antonio, Texas, USA
| | - Hugo Ricardo Navarro-Contreras
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luís Potosí, San Luis Potosí, México
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7
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Hernández-Arteaga AC, de Jesús Zermeño-Nava J, Martínez-Martínez MU, Hernández-Cedillo A, Ojeda-Galván HJ, José-Yacamán M, Navarro-Contreras HR. Determination of Salivary Sialic Acid Through Nanotechnology: A Useful Biomarker for the Screening of Breast Cancer. Arch Med Res 2019; 50:105-110. [DOI: 10.1016/j.arcmed.2019.05.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Revised: 05/22/2019] [Accepted: 05/30/2019] [Indexed: 10/26/2022]
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The serum SA levels are significantly increased in sepsis but decreased in cirrhosis. PROGRESS IN MOLECULAR BIOLOGY AND TRANSLATIONAL SCIENCE 2019; 162:335-348. [PMID: 30905461 DOI: 10.1016/bs.pmbts.2019.01.009] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Most of proteins in human blood circulation are glycoproteins with one or more covalently linked N- or O-linked glycans. Sialic acid (SA) generally occurs as the terminal monosaccharide on the glycans. SA in glycoproteins modulates a wide range of physiological and pathological processes and has been routinely measured in hospital since 1950s. Increased serum SA levels have been associated with different types of cancers. However, a systematic comparison of the serum SA levels in different types of human diseases has not been reported. In current study, 160,537 clinical lab test results of serum SA levels from healthy individuals and patients with 64 different types of diseases during the past 5 years in our hospital were retrieved and analyzed. Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering 55 different types of cancer and noncancer diseases such as sepsis, pancreatitis, bone cancer, rheumatoid arthritis, pancreatic cancer, and encephalitis had significantly (p<0.05, -Log10p>1.30) increased median serum SA levels whereas patients suffering hepatic encephalopathy, cirrhosis, renal cyst, and hepatitis had significantly decreased median serum SA levels compared to that of healthy controls. Moreover, the greatest increase in the mean (SD) and -Log10p values was observed in sepsis and pancreatitis, respectively, but not in cancers. Thus, the regulations of serum SA levels were much more complicated than previously assumed. Understanding the molecular mechanisms behind these observations would make serum SA a useful biomarker to facilitate personalized diagnosis and treatment for patients with different diseases.
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Gruszewska E, Cylwik B, Gudowska M, Panasiuk A, Flisiak R, Chrostek L. The concentration of total sialic acid in chronic hepatitis B and C. Ann Clin Biochem 2018; 56:118-122. [PMID: 30027776 DOI: 10.1177/0004563218792292] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND The synthesis and glycosylation of glycoproteins and glycolipids take place in the liver. Thus, liver diseases may affect serum concentrations of some carbohydrate derivatives, especially the concentration of sialic acid which is attached to the end of oligosaccharide chains. The aim of this study was to measure and compare the serum concentration of total sialic acid in chronic hepatitis B and C. The hypothesis is that both viruses responsible for the development of inflammation work differently at the cellular level. METHODS Serum samples were obtained from 90 patients suffering from liver diseases: 50 from chronic hepatitis B and 40 from chronic hepatitis C at the time of diagnosis. The total sialic acid concentration in the serum was measured according to the enzymatic method using a colorimetric procedure. RESULTS The mean total sialic acid concentration in patients with chronic hepatitis B was significantly lower than the mean concentration in the healthy group, while in patients with chronic hepatitis C, it was significantly higher than that in healthy people and in patients suffering from chronic hepatitis B. There were no significant differences in total sialic acid concentrations in patients with chronic hepatitis B and C according to the grade of portal/periportal activity, the grade of lobular activity and the stage of fibrosis. CONCLUSIONS We conclude that chronic viral hepatitis affects the total serum concentration of sialic acid. Moreover, the concentration of total sialic acid may be a useful marker to differentiate between chronic hepatitis B and C but is not useful for evaluation of the progression of these diseases.
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Affiliation(s)
- Ewa Gruszewska
- 1 Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok, Poland
| | - Bogdan Cylwik
- 2 Department of Pediatric Laboratory Diagnostics, Medical University of Bialystok, Bialystok, Poland
| | - Monika Gudowska
- 1 Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok, Poland
| | - Anatol Panasiuk
- 3 Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
| | - Robert Flisiak
- 3 Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
| | - Lech Chrostek
- 1 Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok, Poland
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Zermeño-Nava JDJ, Martínez-Martínez MU, Rámirez-de-Ávila AL, Hernández-Arteaga AC, García-Valdivieso MG, Hernández-Cedillo A, José-Yacamán M, Navarro-Contreras HR. Determination of sialic acid in saliva by means of surface-enhanced Raman spectroscopy as a marker in adnexal mass patients: ovarian cancer vs benign cases. J Ovarian Res 2018; 11:61. [PMID: 30041680 PMCID: PMC6058371 DOI: 10.1186/s13048-018-0433-9] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2018] [Accepted: 07/12/2018] [Indexed: 12/26/2022] Open
Abstract
Background To demonstrate the use of surface-enhanced Raman spectroscopy (SERS) to determine sialic acid (SA) levels in saliva using silver nanoparticles as substrates, in adnexal mass patients scheduled for surgical intervention to remove invasive masses, with the aim to compare SA levels in benign tumor vs ovarian cancer patients. Methods Quantification of SA levels was accomplished by measuring their SERS and calibrating with analytical reagent SA. The mean SA concentration in saliva from 37 benign adnexal mass resulted smaller (5.1 mg/dL) than the mean concentration in 15 Ovarium cancer patients (23 mg/dL). The cancer condition was determined by biopsy of the removed adnexal mass. The CA-125 biomarker was also measured. The predictive potential of both biomarkers is discussed, together with the malignity risk index (MRI). Results Our results showed a sensitivity/specificity of 80%/100% with a cutoff to distinguish between benign/cancer cases of SA 15.5 mg/dL, as established from a ROC analysis. Our results suggest that SA may be a more useful biomarker than CA-125 to detect ovarian cancer. Conclusions Our results suggest that the SA levels measured from saliva may be as good predictors as the MRI index for the presence of ovarian cancer in sensitivity/negative predictive value and outperforms it in specificity/positive predictive value. Electronic supplementary material The online version of this article (10.1186/s13048-018-0433-9) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- José de Jesús Zermeño-Nava
- División de Gineco-Obstetricia, Hospital Central Dr. Ignacio Morones Prieto, Ave. Venustiano Carranza 2395, Zona Universitaria, 78290, San Luis Potosí, SLP, Mexico
| | - Marco Ulises Martínez-Martínez
- División de Gineco-Obstetricia, Hospital Central Dr. Ignacio Morones Prieto, Ave. Venustiano Carranza 2395, Zona Universitaria, 78290, San Luis Potosí, SLP, Mexico.,Hospital General de Zona No.1, Instituto Mexicano del Seguro Social (IMSS), San Luis Potosí, SLP, Mexico
| | - Ana Laura Rámirez-de-Ávila
- División de Gineco-Obstetricia, Hospital Central Dr. Ignacio Morones Prieto, Ave. Venustiano Carranza 2395, Zona Universitaria, 78290, San Luis Potosí, SLP, Mexico
| | - Aida Catalina Hernández-Arteaga
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luís Potosí, Álvaro Obregón 64, 78000, San Luis Potosí, SLP, Mexico
| | - Ma Guadalupe García-Valdivieso
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luís Potosí, Álvaro Obregón 64, 78000, San Luis Potosí, SLP, Mexico.
| | - Alondra Hernández-Cedillo
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luís Potosí, Álvaro Obregón 64, 78000, San Luis Potosí, SLP, Mexico
| | - Miguel José-Yacamán
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luís Potosí, Álvaro Obregón 64, 78000, San Luis Potosí, SLP, Mexico.,Department of Physics and Astronomy, University of Texas at San Antonio, San Antonio, TX, 78249, USA
| | - Hugo Ricardo Navarro-Contreras
- Coordinación para la Innovación y Aplicación de la Ciencia y la Tecnología (CIACYT), Universidad Autónoma de San Luís Potosí, Álvaro Obregón 64, 78000, San Luis Potosí, SLP, Mexico.
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11
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Zhang Z, Wuhrer M, Holst S. Serum sialylation changes in cancer. Glycoconj J 2018; 35:139-160. [PMID: 29680984 PMCID: PMC5916985 DOI: 10.1007/s10719-018-9820-0] [Citation(s) in RCA: 127] [Impact Index Per Article: 18.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2017] [Revised: 02/14/2018] [Accepted: 03/26/2018] [Indexed: 12/17/2022]
Abstract
Cancer is a major cause of death in both developing and developed countries. Early detection and efficient therapy can greatly enhance survival. Aberrant glycosylation has been recognized to be one of the hallmarks of cancer as glycans participate in many cancer-associated events. Cancer-associated glycosylation changes often involve sialic acids which play important roles in cell-cell interaction, recognition and immunological response. This review aims at giving a comprehensive overview of the literature on changes of sialylation in serum of cancer patients. Furthermore, the methods available to measure serum and plasma sialic acids as well as possible underlying biochemical mechanisms involved in the serum sialylation changes are surveyed. In general, total serum sialylation levels appear to be increased with various malignancies and show a potential for clinical applications, especially for disease monitoring and prognosis. In addition to overall sialic acid levels and the amount of sialic acid per total protein, glycoprofiling of specific cancer-associated glycoproteins, acute phase proteins and immunoglobulins in serum as well as the measurements of sialylation-related enzymes such as sialidases and sialyltransferases have been reported for early detection of cancer, assessing cancer progression and improving prognosis of cancer patients. Moreover, sialic-acid containing glycan antigens such as CA19-9, sialyl Lewis X and sialyl Tn on serum proteins have also displayed their value in cancer diagnosis and management whereby increased levels of these factors positively correlated with metastasis or poor prognosis.
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Affiliation(s)
- Zejian Zhang
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Postzone S3, Postbus 9600, 2300 RC, Leiden, NL, The Netherlands.,Department of Biochemistry and Molecular Biology, Key Laboratory of Glycoconjugate Research Ministry of Public Health, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Manfred Wuhrer
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Postzone S3, Postbus 9600, 2300 RC, Leiden, NL, The Netherlands
| | - Stephanie Holst
- Center for Proteomics and Metabolomics, Leiden University Medical Center, Postzone S3, Postbus 9600, 2300 RC, Leiden, NL, The Netherlands.
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12
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Gornati R, Rapelli S, Montorfano G, Cattaneo C, Berra B. A New Procedure for Gangliosidic N-Acetylneuraminic Acid Analysis in Serum. Int J Biol Markers 2018; 6:91-8. [PMID: 1890318 DOI: 10.1177/172460089100600202] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
In this paper a method is presented which is suitable for the extraction, purification and analysis of serum gangliosides. The advantage in comparison with other previously published procedures is the complete extraction of sialoglycolipids without contamination of sialoglycoproteins and/or sialoglycopeptides. The method could be used as a second-level test for the diagnosis and follow-up of cancer patients, and also could be potentially used for pharmaco-kinetic studies after ganglioside treatment.
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Affiliation(s)
- R Gornati
- Institute of General Physiology and Biological Chemistry, School of Pharmacy, University of Milano, Italy
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13
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Gruszewska E, Chrostek L. Serum Sialic Acid as a Biomarker in Liver Disease. BIOMARKERS IN DISEASE: METHODS, DISCOVERIES AND APPLICATIONS 2017. [DOI: 10.1007/978-94-007-7675-3_11] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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14
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Terzioglu D, Uslu L, Simsek G, Atukeren P, Erman H, Gelisgen R, Ayvaz S, Aksu B, Uzun H. The Effects of Hyperbaric Oxygen Treatment on Total Antioxidant Capacity and Prolidase Activity after Bile Duct Ligation in Rats. J INVEST SURG 2016; 30:376-382. [DOI: 10.1080/08941939.2016.1257666] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Duygu Terzioglu
- Department of Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Lebriz Uslu
- Department of Nuclear Medicine, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul Turkey
| | - Gonul Simsek
- Department of Physiology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Pinar Atukeren
- Department of Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Hayriye Erman
- Department of Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Remise Gelisgen
- Department of Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Suleyman Ayvaz
- Department of Pediatric Surgery, Faculty of Medicine, Trakya University, Edirne, Turkey
| | - Burhan Aksu
- Department of Pediatric Surgery, Faculty of Medicine, Trakya University, Edirne, Turkey
| | - Hafize Uzun
- Department of Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
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15
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Total and free serum sialic acid concentration in liver diseases. BIOMED RESEARCH INTERNATIONAL 2014; 2014:876096. [PMID: 24959592 PMCID: PMC4052165 DOI: 10.1155/2014/876096] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Revised: 04/16/2014] [Accepted: 04/28/2014] [Indexed: 11/18/2022]
Abstract
Background. The objective of this study was to compare the levels of total (TSA) and free (FSA) sialic acid in acute and chronic liver diseases. Materials and Methods. The serum TSA and FSA levels were determined in 278 patients suffering from acute and chronic liver diseases of different etiologies. TSA was estimated by enzymatic method and FSA by the thiobarbituric method modified by Skoza and Mohos. Results. There were no significant differences in the serum TSA concentration between liver diseases of different etiologies, although in most of the liver diseases the mean TSA level was significantly lower than that in the control group. In contrast to TSA, the concentration of FSA appears to differ between liver diseases. In toxic hepatitis it was higher than that in nonalcoholic cirrhosis. However, neither of them differs between alcoholic and nonalcoholic cirrhosis or between liver tumors and tumors with cirrhosis. Conclusions. We conclude that the changes in concentrations of TSA and FSA during the same liver diseases indicate significant disturbances in sialylation of serum glycoproteins.
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16
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Chrostek L, Supronowicz L, Panasiuk A, Cylwik B, Gruszewska E, Szmitkowski M. Serum sialic acids levels according to the severity of liver cirrhosis. J Clin Lab Anal 2014; 28:465-8. [PMID: 24659250 DOI: 10.1002/jcla.21711] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2012] [Accepted: 10/02/2013] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND The sialylation of serum proteins and lipids changes in liver diseases of different etiologies and could change the total sialic acid (TSA), lipid-bound SA (LSA), and free SA (FSA) levels in the sera. However, little is known of the relationship of serum SAs concentrations and the severity of liver disease. Therefore, the aim of this study was to investigate the SAs concentrations (TSA, LSA, and FSA) in liver cirrhosis in relation with the severity of liver disease. METHODS Tested group consisted of 91 consecutive patients suffering from liver cirrhosis. For each patient, the Child-Pugh score was calculated. TSA and LSA were determined by the enzymatic method on microplate reader, and FSA using the thiobarbituric method. RESULTS Among the SA forms, only the serum FSA level in liver cirrhosis appears to be different according to the severity of liver damage evaluated by the Child-Pugh score. It was the highest in score C, and was higher than that in scores B and A. The elevated levels of FSA significantly positively correlated with the Child-Pugh score. CONCLUSION In conclusion, the sialylation of serum proteins and lipids changes in liver cirrhosis, but only the serum concentrations of FSA are stage-related and reflect the severity of liver disease.
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Affiliation(s)
- Lech Chrostek
- Department of Biochemical Diagnostics, Medical University of Bialystok, Bialystok, Poland
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17
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Hassan AM, El-Shenawee M. Modeling Biopotential Signals and Current Densities of Multiple Breast Cancerous Cells. IEEE Trans Biomed Eng 2010; 57:2099-106. [DOI: 10.1109/tbme.2010.2049575] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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18
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Nazifi S, Ansari-Lari M, Ghafari N, Mohtarami S, Ghezelbash A, Tabandeh MR. Evaluation of sialic acids, TNF-α, INF-γ, and acute-phase proteins in cattle infected with foot-and-mouth disease. ACTA ACUST UNITED AC 2010. [DOI: 10.1007/s00580-010-1059-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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19
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Cylwik B, Chrostek L, Panasiuk A, Szmitkowski M. Serum total and free sialic acid in patients with chronic liver disease. Clin Chem Lab Med 2010; 48:137-9. [DOI: 10.1515/cclm.2010.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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20
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Evaluation of sialic acid and acute-phase proteins (haptoglobin and serum amyloids A) in healthy and avian infection bronchitis virus-infected chicks. ACTA ACUST UNITED AC 2009; 20:69-73. [PMID: 32214968 PMCID: PMC7088070 DOI: 10.1007/s00580-009-0939-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2009] [Accepted: 11/18/2009] [Indexed: 11/17/2022]
Abstract
Forty-five 24-day-old Cobb chicks infected with infectious bronchitis virus (IBV) and ten healthy 24-day-old Cobb chicks without any clinical signs of IBV as control group were selected for the study. All of the diseased chicks showed some or all of the clinical signs of infectious bronchitis including gasping, coughing and nasal discharge, wet eyes, swollen sinuses, reduction of food consumption and weight gain. Diagnosis of IBV was based on clinical signs and ELISA test. Blood samples were taken from the wing vein into two tubes: one containing ethylenediaminetetraacetic acid (EDTA) and one without EDTA. Haptoglobin (Hp), serum amyloid A (SAA), total sialic acid (TSA), lipid-bound sialic acid (LBSA) and protein-bound sialic acid (PBSA) concentrations were measured. All of the study variables were significantly higher in diseased birds compared with control group. Results showed that there were significant positive correlations between TSA, LBSA and PBSA in both groups. No correlation was observed between Hp and SAA with any other parameters; however, there was significant negative correlation between Hp and SAA in the control group. Results for receiver operating characteristic analysis showed that area under the curve (AUC) for TSA, LBSA, PBSA, Hp and SAA were 0.93, 0.98, 0.90, 0.90 and 0.80, respectively. According to AUC, LBSA was the most sensitive factor to change in the diseased birds. It can be concluded that in naturally occurring IBV infection, significant increases in TSA, LBSA, PBSA, Hp and SAA concentrations are expected and among study variables, LBSA had the most obvious change so it may be considered as the most sensitive parameter.
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21
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Vitaioli L, Baldoni E, Indraccolo SR, Antuzzi D, Ricci R. Evaluation of sialic acid and α-neuraminidase activity in normal and pathological endometrium. J OBSTET GYNAECOL 2009. [DOI: 10.3109/01443619609020729] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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22
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Inaba H, Nakano K, Kato T, Nomura R, Kawai S, Kuboniwa M, Ishihara K, Ooshima T, Amano A. Heterogenic virulence and related factors among clinical isolates of Porphyromonas gingivalis with type II fimbriae. ACTA ACUST UNITED AC 2008; 23:29-35. [PMID: 18173795 DOI: 10.1111/j.1399-302x.2007.00386.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND/AIMS Porphyromonas gingivalis is a periodontal pathogen whose fimbriae are classified into six genotypes (types I-V and Ib) based on the diversity of the fimA genes encoding the fimbrial subunits. Accumulated evidence suggests that P. gingivalis strains with type II fimbriae are more virulent as compared to those with other types. However, it is unknown if strong virulence is uniformly conserved among clones with type II fimbriae. In the present study, we compared infectious inflammatory changes in clinical isolates of P. gingivalis with type II fimbriae using a mouse abscess model to examine their pathogenic heterogeneity and heterogeneity-related factors. METHODS Suspensions of nine different clinical isolates with type II fimbriae were subcutaneously injected into female BALB/c mice and inflammatory parameters, such as serum sialic acid concentration, were compared. RESULTS Many of the type II fimbrial isolates caused severe inflammation in the mice, though some were less causative, as was the control strain ATCC 33277 (type I fimbria strain). These results showed that pathogenic heterogeneity exists among P. gingivalis clones with type II fimbriae. Further, the heterogeneity-related factors of P. gingivalis strains were analyzed and the pathogenic potentials showed positive relationships to gingipain activities and invasive efficiency but not to hydrophobicity or autoaggregation. In addition, invasive efficiency was related to the activities of gingipains that were extracellularly secreted. CONCLUSION These results suggest that pathogenic heterogeneity has relationships with the invasive and proteolytic activities of P. gingivalis clones with type II fimbriae.
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Affiliation(s)
- H Inaba
- Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka, Japan
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23
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Erdogan HM, Karapehlivan M, Citil M, Atakisi O, Uzlu E, Unver A. Serum sialic acid and oxidative stress parameters changes in cattle with leptospirosis. Vet Res Commun 2008; 32:333-9. [DOI: 10.1007/s11259-008-9036-z] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2007] [Accepted: 01/14/2008] [Indexed: 10/22/2022]
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24
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Cylwik B, Chrostek L, Zalewski B, Dabrowski A, Szmitkowski M. Serum total sialic acid in differential diagnostics of jaundice caused by malignant and nonmalignant diseases: a ROC curve analysis. Dig Dis Sci 2007; 52:2317-22. [PMID: 17406834 DOI: 10.1007/s10620-006-9640-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2006] [Accepted: 10/09/2006] [Indexed: 12/09/2022]
Abstract
The purpose of this study was to evaluate the usefulness of serum total sialic acid (SA) for discrimination of malignant and nonmalignant jaundice. Serum SA concentration and its ratio with total protein (SA/TP) were determined in 55 patients with jaundice: 25 malignant and 30 nonmalignant. SA was estimated by enzymatic method. Serum total SA and the ratio SA/TP were significantly higher in malignant than in nonmalignant jaundice. Diagnostic sensitivity of SA and the ratio of SA/TP in both types of jaundice reached the value of 95.8%. The specificity, positive and negative predictive values, and efficiency of SA and SA/TP were higher in malignant than in nonmalignant jaundice. Areas under ROC curves for SA and the ratio of SA/TP in malignant jaundice were higher than in nonmalignant, but there were not statistically significant differences. SA levels and the ratio of SA/TP do not have the ability to discriminate between these types of jaundice.
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Affiliation(s)
- Bogdan Cylwik
- Department of Biochemical Diagnostics, Medical University, Bialystok, Poland
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25
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Karapehlivan M, Atakisi E, Citil M, Kankavi O, Atakisi O. Serum sialic acid levels in calves with pneumonia. Vet Res Commun 2006; 31:37-41. [PMID: 17180455 DOI: 10.1007/s11259-006-3312-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/12/2005] [Indexed: 10/23/2022]
Affiliation(s)
- M Karapehlivan
- Department of Biochemistry, Faculty of Veterinary Medicine, University of Kafkas, Kars.
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26
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Tzanakakis GN, Syrokou A, Kanakis I, Karamanos NK. Determination and distribution of N-acetyl- and N-glycolylneuraminic acids in culture media and cell-associated glycoconjugates from human malignant mesothelioma and adenocarcinoma cells. Biomed Chromatogr 2006; 20:434-9. [PMID: 16177958 DOI: 10.1002/bmc.573] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Sialic acids containing glycoconjugates are very common in human neoplasias and their expression frequently correlates with malignant phenotype and the tumor grade. The majority of tumor markers containing sialic acids in man involve changes in the amount of total sialic acids and in the presence of the two main sialic acid types, Neu5Ac and Neu5Gc, and their derivatives. The aim of the present study was to examine whether malignant mesothelioma cell lines synthesize sialic acid containing glycoconjugates at both the extracellular and cell membrane levels and particularly whether the type and the content of Neu5Ac and Neu5Gc are of biological importance for mesothelioma cell differentiation and evaluation of its prognosis. The study was performed in three human malignant mesothelioma cell lines, two with a fibroblast like phenotype (STAV-FCS and Vester) and one of epithelial differentiation (STAV-AB), which developed from the pleural effusions of patients with malignant mesothelioma and in one human adenocarcinoma cell line (Wart). Neu5Ac and Neu5Gc were determined following a mild hydrolysis step and a sample clean-up procedure. The determination was performed by reversed-phase HPLC after the NeuAc and NeuGc had been converted to per-O-benzoylated derivatives. It was found that Neu5Gc is the major sialic acid in the culture media of all cell lines examined. Molar ratios of Neu5Ac to Neu5Gc showed that Neu5Gc is the predominant sialic acid in the culture medium of the fibroblast-like mesothelioma cells. Neu5Ac is almost undetectable in the cell membrane, whereas Neu5Gc is present in considerable amounts. The obtained results suggest that the type and the content of Neu5Ac and Neu5Gc in culture media are of biological importance for mesothelioma cell differentiation and may be of value in the evaluation of prognosis.
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Affiliation(s)
- G N Tzanakakis
- Department of Histology and Anatomy, School of Medicine, University of Crete, 71110 Heraklion, Greece.
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27
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Munday K, Ginty F, Fulford A, Bates CJ. Relationships between biochemical bone turnover markers, season, and inflammatory status indices in prepubertal Gambian boys. Calcif Tissue Int 2006; 79:15-21. [PMID: 16868668 DOI: 10.1007/s00223-005-0276-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2005] [Accepted: 04/08/2006] [Indexed: 10/24/2022]
Abstract
Seasonal and interindividual differences in food availability and illnesses cause variations in growth, including bone growth, in children in developing countries. We investigated seasonal differences in biochemical (serum) markers of bone metabolism and relationships between these markers (procollagen type I N propeptide [P1NP], serum C-terminal telopeptide of type 1 collagen [S-CTX]) and serum markers of inflammation (alpha(1)- antichymotrypsin [ACT], C-reactive protein [CRP], sialic acid) in prepubertal Gambian boys. Three seasonal time points were chosen: August, mid-rainy season; October, late rainy season (both are associated with decreased food supply, increased prevalence of infection, reduced weight gain, and stunting); and April, late dry season, when environmental conditions are better and rates of weight gain are higher. The prevalence of raised inflammatory markers was high: 29% of ACT values >0.40 g/L in August, 42% >0.40 g/L in October, and 18% >0.40 g/L in April. Of CRP values, 92-96% were >0.47 mg/L and 30%, 46%, and 18% were >3.95 mg/L in August, October, and April, respectively. Also, 42-52% of sialic acid values were >648 mg/L. Of the bone markers, S-CTX exhibited the highest values in August; P1NP did not vary with season. Inverse relationships between each bone marker and the acute phase markers occurred, with the strongest relationships between P1NP and ACT or sialic acid. We conclude that bone collagen synthesis and turnover are reduced during inflammation in rural Gambian boys. Biochemical indices can provide powerful, single-time point evidence of infection and growth-faltering episodes.
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Affiliation(s)
- K Munday
- Elsie Widdowson Laboratory, MRC Human Nutrition Research, Fulbourn Road, Cambridge CB1 9NL, United Kingdom
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Nakano K, Tsuji M, Nishimura K, Nomura R, Ooshima T. Contribution of cell surface protein antigen PAc of Streptococcus mutans to bacteremia. Microbes Infect 2006; 8:114-21. [PMID: 16442486 DOI: 10.1016/j.micinf.2005.06.005] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2005] [Revised: 05/21/2005] [Accepted: 06/02/2005] [Indexed: 11/23/2022]
Abstract
Streptococcus mutans, a major cariogenic bacterium, is occasionally isolated from the blood of patients with bacteremia and infective endocarditis. Mutant strains of S. mutans MT8148, defective in the major surface proteins glucosyltransferase (GTF) B-, C-, and D-, and protein antigen c (PAc), were constructed by insertional inactivation of each respective gene with an antibiotic resistant cassette. Susceptibility to phagocytosis was determined by analyses of interactions of the bacteria with human polymorphonuclear leukocytes, and the PAc-defective mutant strain (PD) showed the lowest rate of phagocytosis. Further, when PD and MT8148 were separately injected into the jugular veins of Sprague-Dawley rats, PD was recovered in significantly larger numbers and for a longer duration, and caused more severe systemic inflammation than MT8148, indicating that S. mutans PAc is associated with its systemic virulence in blood. Next, 100 S. mutans clinical isolates from 100 Japanese children and adolescents were analyzed by Western blotting using antisera raised against recombinant PAc, generated based on the pac sequence of MT8148. Four of the 100 strains showed no positive band and each exhibited a significantly lower phagocytosis rate than that of 25 randomly selected clinical strains (P < 0.01). In addition, three of the 100 strains possessed a lower molecular weight PAc and a significantly lower rate of phagocytosis than the 25 reference strains (P < 0.05). These results suggest that S. mutans PAc may be associated with phagocytosis susceptibility to human polymorphonuclear leukocytes, with approximately 7% of S. mutans clinical isolates possible high-risk strains for the development of bacteremia.
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Affiliation(s)
- Kazuhiko Nakano
- Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry, Osaka 565-0871, Japan
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29
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Eguchi H, Ikeda Y, Ookawara T, Koyota S, Fujiwara N, Honke K, Wang PG, Taniguchi N, Suzuki K. Modification of oligosaccharides by reactive oxygen species decreases sialyl lewis x-mediated cell adhesion. Glycobiology 2005; 15:1094-101. [PMID: 16000697 DOI: 10.1093/glycob/cwj003] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Modification of cell surface oligosaccharides by reactive oxygen species (ROS) and the biological effect of such modifications on cell adhesion were investigated. Treatment of HL60, a human promyelocyte leukemia cell line, with ROS, generated by a combination of hypoxanthine and xanthine oxidase (HX/XO), decreased the sialic acid content on the cell surface, as indicated by a flow cytometric analysis involving sialic acid-specific lectins, and a concomitant increase of free sialic acid was observed in the supernatant. A cell adhesion assay showed that the HX/XO treatment of HL60 cells decreases their capability of binding to human umbilical vein endothelial cells (HUVEC), probably because of an impairment of the interaction involving E-selectin, whereas the decrease in the binding was canceled by the addition of superoxide dismutase (SOD) and catalase. In fact, cell surface sialyl lewis x (sLe x), but not lewis x (Le x), was decreased by HX/XO treatment. Thus, it is more likely that the impaired interaction is based on diminished levels of the selectin ligand. Cleavage of sialic acid by ROS was further verified by the degradation of 4MU-Neu5Ac by HX/XO in the presence of hydrogen peroxide and iron ion. These results indicate that glycosidic linkage of sialic acid is a potential target for superoxide and other related ROS. It is well known that ROS cause cellular damages such as lipid peroxidation and protein oxidation, but, as suggested by the findings reported in the literature, ROS may also regulate cell adhesion via the structural alteration of sialylated oligosaccharides on the cell surface.
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Affiliation(s)
- Hironobu Eguchi
- Department of Biochemistry, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya, Hyogo 663-8501, Japan
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Nakano K, Fujita K, Nishimura K, Nomura R, Ooshima T. Contribution of biofilm regulatory protein A of Streptococcus mutans, to systemic virulence. Microbes Infect 2005; 7:1246-55. [PMID: 16039152 DOI: 10.1016/j.micinf.2005.04.012] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2005] [Revised: 03/25/2005] [Accepted: 04/13/2005] [Indexed: 11/27/2022]
Abstract
Streptococcus mutans is occasionally isolated from the blood of patients with bacteremia and infective endocarditis (IE), and the possibility that it could be pathogenic for those diseases has been discussed. The initial important step for the involvement of bacterial pathogens in the virulence of IE is thought to be survival in blood for an extended period. Recently, the brpA gene encoding biofilm regulatory protein A (BrpA) of S. mutans was cloned and sequenced, after which it was shown that inactivation of brpA in an isogenic mutant strain resulted in longer chain formation than in the parental strain. In the present study, a BrpA-defective isogenic mutant strain (MT8148BRD) was constructed from strain MT8148. In an analysis of its susceptibility to phagocytosis by human polymorphonuclear leukocytes (PMNs), the phagocytosis rate of MT8148BRD was shown to be significantly lower than that of MT8148 (P < 0.01). Next, strains with various chain lengths were produced by culturing MT8148 in media with various initial pH levels, which revealed that there was a statistically negative correlation between phagocytosis susceptibility and chain length (P < 0.01). Further, MT8148BRD was found to possess higher platelet aggregation properties than MT8148 (P < 0.05). In addition, injection of MT8148BRD into the jugular vein of specific pathogen-free Sprague-Dawley rats resulted in a longer duration of bacteremia, which prolonged systemic inflammation for a longer period than in those infected with MT8148. These results indicate that S. mutans BrpA is associated with virulence in blood, due to its correlation to phagocytosis susceptibility and platelet aggregation properties.
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Affiliation(s)
- Kazuhiko Nakano
- Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry, 1-8 Yamada-oka, Suita, Osaka 565-0871, Japan
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31
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Nomura R, Nakano K, Ooshima T. Contribution of glucan-binding protein C of Streptococcus mutans to bacteremia occurrence. Arch Oral Biol 2004; 49:783-8. [PMID: 15308422 DOI: 10.1016/j.archoralbio.2004.04.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2004] [Indexed: 11/26/2022]
Abstract
Our previous analysis of major cell surface proteins of Streptococcus mutans isolated from the blood of a patient with bacteremia showed variations of glucan-binding protein C (GbpC) expression. In the present study, we analyzed the contribution of GbpC of S. mutans to bacteremia occurrence. A GbpC-defective mutant strain (C1) was significantly less susceptible to phagocytosis by human polymorphonuclear leukocytes than its parent strain (MT8148) (P < 0.001). When 21 rats were injected with C1 or streptomycin-resistant MT8148R into the jugular vein, strain C1 was recovered from blood in larger numbers and for a longer duration than MT8148R. Further, infection with C1 resulted in significant increases in serum sialic acid (SSA) concentrations, and splenomegaly, as well as body weight reduction. We also evaluated GbpC expression in 20 clinical oral isolates by immunoblotting with anti-GbpC serum, and found that expression intensity was positively correlated to phagocytosis rate (P < 0.05). These results suggest that S. mutans GbpC may be associated with systemic virulence, since a weak expression of GbpC causes the organisms to be refractory to phagocytosis, resulting in a longer survival of the bacterium in the bloodstream.
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Affiliation(s)
- R Nomura
- Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry, 1-8 Yamada-oka, Suita, 565-0871, Japan
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Nakano K, Kuboniwa M, Nakagawa I, Yamamura T, Nomura R, Okahashi N, Ooshima T, Amano A. Comparison of inflammatory changes caused by Porphyromonas gingivalis with distinct fimA genotypes in a mouse abscess model. ACTA ACUST UNITED AC 2004; 19:205-9. [PMID: 15107074 DOI: 10.1111/j.0902-0055.2004.00133.x] [Citation(s) in RCA: 65] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
The fimA gene of Porphyromonas gingivalis, encoding fimbrillin (a subunit protein of fimbriae) has been classified into six genotypes (types I-V and Ib). The genotypic variation was previously suggested to be related to the severity of adult periodontitis in the general population. In this study, we compared inflammatory changes caused by bacterial infection to study pathogenic heterogeneity among the different fimA strains in a mouse abscess model. Bacterial suspensions of 13 P. gingivalis strains representing the six fimA types were subcutaneously injected into female BALB/c mice, and serum sialic acid concentrations were assayed as a quantitative host inflammatory parameter. Type II fimA organisms caused the most significant induction of serum sialic acid, as well as other infectious symptoms, followed by types Ib, IV and V. In contrast, types I and III caused weak inflammatory changes. In addition, fimA mutants of type II strains clearly lost their infectious ability. These findings suggest that fimA genotypic variation affects expression of P. gingivalis virulence.
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Affiliation(s)
- K Nakano
- Department of Pediatric Dentistry, Osaka University Graduate School of Dentistry, Osaka, Japan.
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Sakurai A, Okahashi N, Nakagawa I, Kawabata S, Amano A, Ooshima T, Hamada S. Streptococcus pyogenes infection induces septic arthritis with increased production of the receptor activator of the NF-kappaB ligand. Infect Immun 2003; 71:6019-26. [PMID: 14500523 PMCID: PMC201078 DOI: 10.1128/iai.71.10.6019-6026.2003] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Bacterial arthritis is a rapidly progressive and highly destructive joint disease in humans, with Staphylococcus aureus and Neisseria gonorrhoeae the major causative agents, although beta-hemolytic streptococci as well often induce the disease. We demonstrate here that intravenous inoculation of CD-1 mice with the group A streptococcus (GAS) species Streptococcus pyogenes resulted in a high incidence of septic arthritis. Signs of arthritis emerged within the first few days after injection, and bacterial examinations revealed that colonization of the inoculated GAS in the arthritic joints persisted for 21 days. Induction of persistent septic arthritis was dependent on the number of microorganisms inoculated. Immunohistochemical staining of GAS with anti-GAS antibodies revealed colonization in the joints of infected mice. Cytokine levels were quantified in the joints and sera of infected mice by using an enzyme-linked immunosorbent assay. High levels of interleukin-1beta (IL-1beta) and IL-6 were detected in the joints from 3 to 20 days after infection. We noted that an increase in the amount of receptor activator of NF-kappaB ligand (RANKL), which is a key cytokine in osteoclastogenesis, was also evident in the joints of the infected mice. RANKL was not detected in sera, indicating local production of RANKL in the infected joints. Blocking of RANKL by osteoprotegerin, a decoy receptor of RANKL, prevented bone destruction in the infected joints. These results suggest that GAS can colonize in the joints and induce bacterial arthritis. Local RANKL production in the infected joints may be involved in bone destruction.
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Affiliation(s)
- Atsuo Sakurai
- Departments of Oral and Molecular Microbiology, Pediatric Dentistry, Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871, PRESTO, Japan Science and Technology Corporation, Kawaguchi-Saitama 332-0012, Japan
| | - Nobuo Okahashi
- Departments of Oral and Molecular Microbiology, Pediatric Dentistry, Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871, PRESTO, Japan Science and Technology Corporation, Kawaguchi-Saitama 332-0012, Japan
- Corresponding author. Mailing address: Department of Oral Frontier Biology, Osaka University Graduate School of Dentistry, 1-8, Yamadaoka, Suita-Osaka 565-0871, Japan. Phone: 81-6-6879-2976. Fax: 81-6-6879-2976. E-mail:
| | - Ichiro Nakagawa
- Departments of Oral and Molecular Microbiology, Pediatric Dentistry, Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871, PRESTO, Japan Science and Technology Corporation, Kawaguchi-Saitama 332-0012, Japan
| | - Shigetada Kawabata
- Departments of Oral and Molecular Microbiology, Pediatric Dentistry, Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871, PRESTO, Japan Science and Technology Corporation, Kawaguchi-Saitama 332-0012, Japan
| | - Atsuo Amano
- Departments of Oral and Molecular Microbiology, Pediatric Dentistry, Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871, PRESTO, Japan Science and Technology Corporation, Kawaguchi-Saitama 332-0012, Japan
| | - Takashi Ooshima
- Departments of Oral and Molecular Microbiology, Pediatric Dentistry, Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871, PRESTO, Japan Science and Technology Corporation, Kawaguchi-Saitama 332-0012, Japan
| | - Shigeyuki Hamada
- Departments of Oral and Molecular Microbiology, Pediatric Dentistry, Oral Frontier Biology, Osaka University Graduate School of Dentistry, Suita-Osaka 565-0871, PRESTO, Japan Science and Technology Corporation, Kawaguchi-Saitama 332-0012, Japan
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Kongtawelert P, Tangkijvanich P, Ong-Chai S, Poovorawan Y. Role of serum total sialic acid in differentiating cholangiocarcinoma from hepatocellular carcinoma. World J Gastroenterol 2003; 9:2178-2181. [PMID: 14562373 PMCID: PMC4656458 DOI: 10.3748/wjg.v9.i10.2178] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2003] [Revised: 07/25/2003] [Accepted: 08/02/2003] [Indexed: 02/06/2023] Open
Abstract
AIM This study was designed to evaluate the clinical application of serum total sialic acid (TSA) in the diagnosis of cholangiocarcinoma (CCA). METHODS Serum TSA was determined by periodate-resorcinol microassay in 69 patients with CCA, 59 patients with hepatocellular carcinoma (HCC), 37 patients with cirrhosis, 61 patients with chronic hepatitis and 50 healthy blood donors. RESULTS The mean serum TSA concentration in CCA (2.41+/-0.70 mmol/L) was significantly higher than those of HCC, cirrhosis, chronic hepatitis and healthy blood donors (1.41+/-0.37 mmol/L, 1.13+/-0.31 mmol/L, 1.16+/-0.26 mmol/L, and 1.10+/-0.14 mmol/L, respectively; P<0.001). Based on ROC curve analysis, a cut-off point of 1.75 mmol/L discriminated between CCA and HCC with a sensitivity, specificity and accuracy of 82.6 %, 83.1 %, and 82.8 %, respectively. CONCLUSION Based on our results, serum TSA would be a useful marker for the differential diagnosis of CCA from HCC.
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Affiliation(s)
- Prachya Kongtawelert
- Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Thailand
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Takemura Y, Ishida H, Inoue Y. Utilization of common inflammatory markers in new, symptomatic, primary care outpatients based on their cost-effectiveness. Clin Chem Lab Med 2003; 41:668-74. [PMID: 12812265 DOI: 10.1515/cclm.2003.101] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Few studies have demonstrated the optimal usage of common inflammatory markers, alone or in combination, based on the cost-effectiveness. We analyzed the yield and cost of C-reactive protein (CRP), white blood cell count (WBC), erythrocyte sedimentation rate (ESR), sialic acid, and protein fractionation in 177 new primary care outpatients with inflammation-related symptoms. A useful result (UR) was assigned if tests contributed to a change in physician's diagnosis or decision-making. Costs of testing were calculated based on either single or simultaneous measurement. Five inflammatory markers generated 147 URs in 123 patients. CRP showed the best contribution to generation of UR, followed by sialic acid, protein fractionation, WBC, and ESR. CRP demonstrated poor correlation with WBC (r = 0.458), while sialic acid strongly correlated with total absolute amount of alpha1 and alpha2 fractions in protein fractionation (r = 0.855) and moderately with ESR (r = 0.651). The combination of CRP and WBC produced the best cost-effectiveness at a cost of Yen 1169 (US dollars 9.6 or Euro 9.7)/additional UR against CRP testing alone. Sialic acid, an automated multichannel analyzer-based test, demonstrated the favorable cost-effectiveness over ESR or protein fractionation when combined with CRP (and WBC). Our results indicate that the optimal usage of these inflammatory markers should involve careful cost-effectiveness considerations.
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Affiliation(s)
- Yuzuru Takemura
- Department of Laboratory Medicine, National Defense Medical College, Tokorozawa, Saitama, Japan.
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Wongkham S, Bhudhisawasdi V, Chau-in S, Boonla C, Muisuk K, Kongkham S, Wongkham C, Boonsiri P, Thuwajit P. Clinical significance of serum total sialic acid in cholangiocarcinoma. Clin Chim Acta 2003; 327:139-47. [PMID: 12482629 DOI: 10.1016/s0009-8981(02)00371-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND High levels of serum total sialic acid (TSA) have been reported in cholangiocarcinoma (CCA) patients. In this study, the clinical value and possible cause of increased total sialic acid in the serum in cholangiocarcinoma patients were examined. METHODS Total sialic acid was determined in 172 serum and 25 tumor tissue samples taken from cholangiocarcinoma patients using the periodate thiobarbituric acid method. RESULTS The total sialic acid content of the tumor tissue was significantly greater than that of the serum and not related to the concentration found in the serum. The serum total sialic acid was not correlated with age, sex, body mass index, blood group, tumor location, tumor stage, metastatic condition, histological types and survival of the patients. The increased total sialic acid in the serum had a significant correlation with serum MUC5AC mucin, alkaline phosphatase and the CA19-9, and the numbers of white blood cell and neutrophils. CONCLUSIONS The concentration of serum sialic acid was not associated with clinicopathologic features or the tumor burden. The glycoproteins secreted from the tumor and inflammatory cells might be responsible for the increased total sialic acid in the serum in these patients.
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Affiliation(s)
- Sopit Wongkham
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
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Strousopoulou K, Militsopoulou M, Stagiannis K, Lamari FN, Karamanos NK. A capillary zone electrophoresis method for determining N-acetylneuraminic acid in glycoproteins and blood sera. Biomed Chromatogr 2002; 16:146-50. [PMID: 11857648 DOI: 10.1002/bmc.143] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
A simple capillary zone electrophoresis (CZE) method for the determination of the content of the major sialic acid form N-acetylneuraminic acid (Neu5Ac) in glycoproteins was established. The present method utilizes a simplified hydrolysis-purification procedure consisting of mild acid hydrolysis (25 mM trifluoroacetic acid for 2h at 80 degrees C) to release Neu5Ac and ultrafiltration on Centricon-3 membrane to remove the obtained asialoglycoproteins and other macromolecules present in biologic samples. Derivatization with benzoic anhydride at 80 degrees C for 20 min resulted in complete conversion of Neu5Ac to per-O-benzoylated Neu5Ac. CZE analysis was performed using the operating buffer 25mM phosphate, pH 3.5, containing 50% (v/v) acetonitrile as organic modifier at 30 kV, and detection of the per-O-benzoylated Neu5Ac at 231 nm. The method showed excellent repeatability (RDS<1.98%) and a linearity range from 5 microg/mL to 5mg/mL with a detection limit of 2 microM. Application of the method to microanalysis of human alpha(1)-acid glycoprotein and blood serum samples showed excellent agreement with previously published values, suggesting a high precision for the developed CZE method.
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Affiliation(s)
- K Strousopoulou
- Department of Chemistry, Section of Organic Chemistry, Biochemistry and Natural Products, Laboratory of Biochemistry, University of Patras, 26110 Patras, Greece
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Kimura Y, Fujieda S, Takabayashi T, Tanaka T, Sugimoto C, Saito H. Conventional tumor markers are prognostic indicators in patients with head and neck squamous cell carcinoma. Cancer Lett 2000; 155:163-8. [PMID: 10822131 DOI: 10.1016/s0304-3835(00)00423-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
We tested for squamous cell carcinoma-related antigen (SCC), carcinoembryonic antigen (CEA), ferritin, immunosuppressive acid protein (IAP) and sialic acid in the serum from 247 patients with head and neck squamous cell carcinoma prior to therapy. Significant correlations were found between IAP and tumor size, lymph node metastasis, and clinical stage (P<0.0001, P<0.001, and P<0.0001). Also, sialic acid and SCC were also correlated with tumor size, lymph node metastasis, and clinical stage. Moreover IAP, sialic acid and SCC were strongly associated with survival rate (P<0.0001, P = 0.0230 and P = 0.0159). A multivariate Cox proportional hazard model demonstrated that being positive for IAP was an independent predictor for patients with H&NSCC (P = 0.0115). The results indicate that IAP, sialic acid and SCC are useful as prognostic factors.
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Affiliation(s)
- Y Kimura
- Department of Otorhinolaryngology, Fukui Medical University, Shimoaizuki, Matsuoka-cho, Yoshida-gun, 910-1193, Fukui, Japan
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Lu CQ, Lu J, Wang BL, Cui YZ. Changes in ganglioside contents, plasma sialic acid and cAMP levels in experimental hepatoma in mice. Mol Cell Biochem 2000; 207:29-33. [PMID: 10888223 DOI: 10.1023/a:1007029927664] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
The present study was designed to assess whether changes in glycolipids and cyclic AMP contents might serve as markers for the diagnosis of malignancy in the liver. The experimental model was a transplantable murine hepatoma. Experimental mice were divided into three groups: (1) a therapeutic group, which had been transplanted with hepatoma and treated with the antimetabolism drug 5-fluorouracil (0.2 mg/day i.p.), (2) a control group, which had been transplanted with hepatoma and treated with 0.2 ml 0.9% NaCl/day and (3) a normal group of mice. The ganglioside and cAMP contents in the hepatoma tissue, plasma cAMP, total- and lipid-bound sialic acid levels and red blood cell membrane sialic acid levels were determined. Results showed that the ganglioside content, total and lipid-bound sialic acid levels in the control group were significantly higher than those in the livers of normal mice (p < 0.01) while these respective values in the therapeutic group were significantly lower than those in the control group (p < 0.01). The cAMP levels of tumor tissues and plasma in the control group were lower than those in normal mice. No significant difference in red blood cell membrane sialic acid content was observed between the therapeutic and control groups though levels for both were higher than those in normal mice. These results indicate that ganglioside content and sialic acid levels in hepatoma tissues were significantly elevated, and cAMP levels in hepatoma tissues were significantly decreased during proliferation and abnormal differentiation.
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Affiliation(s)
- C Q Lu
- Department of Biochemistry, Wannan Medical College, Wuhu, Anhui, China
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Diamantopoulou S, Stagiannis KD, Vasilopoulos K, Barlas P, Tsegenidis T, Karamanos NK. Importance of high-performance liquid chromatographic analysis of serum N-acylneuraminic acids in evaluating surgical treatment in patients with early endometrial cancer. JOURNAL OF CHROMATOGRAPHY. B, BIOMEDICAL SCIENCES AND APPLICATIONS 1999; 732:375-81. [PMID: 10517360 DOI: 10.1016/s0378-4347(99)00304-7] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The objectives of this study were the quantification of the two major sialic acid (Sia) forms - N-acetylneuraminic (Neu5Ac) and N-glycolylneuraminic acids (Neu5Gc) - in serum before and after surgical treatment of early endometrial cancer and the relation of their levels with the progress of surgical therapy. The major Sia forms were liberated from sera glycoconjugates by mild acid hydrolysis, separated as per-O-benzoylated derivatives by a highly sensitive reversed-phase HPLC method and detected at 231 nm. Total Sia content in sera of healthy women was not related to age and body weight. Neu5Ac was identified as the major Sia in sera from both cancer patients, healthy individuals as well as in tissue specimens (> or = 94% of total Sia). In patients with endometrial cancer the total Sia level before surgical treatment (709.5 +/- 306.5 mg/l) was significantly higher (p < or = 0.0001) than that of the control group (213.5 +/- 88.7 mg/l). The elevation in Sia level was exclusively due to Neu5Ac. Following surgical therapy, serum Neu5Ac levels (699.4 +/- 305.6 mg/l) were significantly decreased (305.9 +/- 114.5 mg/l). In one case, where Neu5Ac level was increased 15 days and eight months after surgery (1.8 and 2.5 times as compared to control, respectively), a metastasis not detected during surgery was recorded. The obtained results suggest that Neu5Ac level in serum may be used as a tumor marker in evaluating the suitability of surgical treatment in early endometrial cancer.
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Abstract
Sialic acid (SA), N-acetylated derivatives of neuraminic acid, play a central role in the biomedical functioning of humans. The normal range of total sialic acid (TSA) level in serum/plasma is 1.58-2.22 mmol L-1, the free form of SA only constituting 0.5-3 mumol L-1 and the lipid-associated (LSA) forms 10-50 mumol L-1. Notably, considerably higher amounts of free SA are found in urine than in serum/plasma (approximately 50% of the total SA). In inherited SA storage diseases such as Salla's disease, SA levels are elevated many times over, and their determination during clinical investigation is well established. Furthermore, a number of reports describe elevated SA levels in various other diseases, tentatively suggesting broader clinical utility for SA markers. Increased SA concentrations have been reported during inflammatory processes, probably resulting from increased levels of richly sialylated acute-phase glycoproteins. A connection between increased SA levels and elevated stroke and cardiovascular mortality risk has also been reported. In addition, SA levels are slightly increased in cancer, positively correlating with the degree of metastasis, as well as in alcohol abuse, diabetes, chronic renal failure and chronic glomerulonephritis. Several different mechanisms are assumed to underlie the elevated SA concentrations in these disorders. The apparent non-specificity of SA to a given disease limits the potential clinical usefulness of SA determination. In addition, some non-pathological factors, such as aging, pregnancy and smoking, may cause changes in SA concentrations. The absolute increases in SA levels are also rather small (save those in inherited SA storage disorders); this further limits the clinical potential of SA as a marker. Tentatively, SA markers might serve as adjuncts, when combined with other markers, in disease screening, disease progression follow-up, and in the monitoring of treatment response. To become clinically useful, however, the existing SA determination assays need to be considerably refined to reduce interferences, to be specific for certain SA forms, and to be more easy to use.
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Thougaard AV, Hellmén E, Jensen AL. Total serum sialic acid is a general disease marker rather than a specific tumour marker in dogs. ZENTRALBLATT FUR VETERINARMEDIZIN. REIHE A 1998; 45:471-9. [PMID: 9838859 DOI: 10.1111/j.1439-0442.1998.tb00850.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The aim of the present study was to examine the levels of total sialic acid (TSA) in serum of clinically healthy dogs and dogs with various diseases to evaluate the usefulness of TSA as a tumour marker. TSA levels in clinically healthy dogs were not different between sexes, but pregnant and lactating dogs had higher mean (+/- standard deviation (SD)) TSA levels than clinically healthy female dogs (642 +/- 78 vs. 495 +/- 73 mg/l, P < 0.001). Eighty-eight dogs with different tumours (54 malignant and 34 benign tumours of different tissues) had higher mean TSA levels than 148 clinically healthy dogs (675 +/- 143 vs. 498 +/- 75 mg/l, P < 0.01). Fifty dogs with other diseases excluding tumours (skin, urinary system, and gastrointestinal diseases, pyometra, other inflammatory diseases, and Cushing's syndrome) had slightly higher TSA levels than the tumour-bearing dogs (730 +/- 159 mg/l, P = 0.02). TSA levels in dogs with malignant tumours did not differ from dogs with benign tumours (682 +/- 144 vs. 664 +/- 142 mg/l, P = 0.73). A receiver-operating characteristic (ROC) plot revealed a maximum sensitivity and specificity combination of 69% and 91% (TSA cut-off concentration 595 mg/l) in distinguishing between healthy dogs and dogs with tumours. When evaluating TSA measurements to distinguish dogs with other diseases from dogs with tumours, a maximum sensitivity and specificity combination of 50% and 75% was found (cut-off concentration 761 mg/l). WHO staging of mammary tumours revealed an increase in TSA levels with increasing stage (P < 0.0001, rs, = 0.62). In conclusion, the nonspecificity of increases makes TSA determinations unsuitable as a tumour marker. TSA levels seem instead to be a general disease marker. Whether serial TSA measurements could be used in the follow-up of dogs operated for malignant tumours should be further investigated.
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Affiliation(s)
- A V Thougaard
- Department of Clinical Studies, Royal Veterinary and Agricultural University, Frederiksberg, Denmark
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Rao VR, Krishnamoorthy L, Kumaraswamy SV, Ramaswamy G. Circulating levels in serum of total sialic acid, lipid-associated sialic acid, and fucose in precancerous lesion and cancer of the oral cavity. CANCER DETECTION AND PREVENTION 1998; 22:237-40. [PMID: 9618045 DOI: 10.1046/j.1525-1500.1998.0oa04.x] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Total sialic acid (TSA), lipid-associated sialic acid (LASA), and fucose were estimated in sera of 35 patients with precancerous lesion of the oral cavity, 68 patients with cancer of the oral cavity, and 25 age- and sex-matched non-chewers of both tobacco and betal nut and nonsmokers as controls. Significant elevation in the serum levels of TSA and LASA were observed in patients with the precancerous and cancer lesions when compared with the controls. Serum TSA levels were elevated significantly in patients with cancer when compared with those with precancerous lesions. Circulating TSA and LASA levels were found to reflect tumor burden and correlated well with stage of the disease. However, serum fucose levels did not show an increase corresponding to stage of the disease. The results suggests that combined evaluation of these markers may be useful in predicting early malignant change and also in assessing the spread and invasiveness of the disease in cancer of the oral cavity.
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Affiliation(s)
- V R Rao
- Department of Biochemistry, Kidwai Memorial Institute of Oncology, Bangalore, India
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Paszkowska A, Berbeć H, Semczuk A, Cybulski M. Sialic acid concentration in serum and tissue of endometrial cancer patients. Eur J Obstet Gynecol Reprod Biol 1998; 76:211-5. [PMID: 9481577 DOI: 10.1016/s0301-2115(97)00176-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Serum total sialic acid (TSA) level was determined in the group of 45 patients with endometrial neoplasia. Moreover, the sialic acid content in 23 surgically obtained tumor tissue specimens has been estimated. The mean value of serum total sialic acid level of the cancer patients (2.38 mmol/l) was significantly higher (P < 0.0001) than the sialic acid level in the control group (1.52 mmol/l). The elevation of serum total sialic acid level was associated with the burden of the tumor (2.30 mmol/l and 2.68 mmol/l for stages I and II + III, respectively). Tissue sialic acid content showed no significant differences between early and advanced clinical stage of the disease.
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Affiliation(s)
- A Paszkowska
- Department of Physiological Chemistry, Lublin School of Medicine, Poland
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Painbeni T, Gamelin E, Cailleux A, Le Bouil A, Boisdron-Celle M, Daver A, Larra F, Allain P. Plasma sialic acid as a marker of the effect of the treatment on metastatic colorectal cancer. Eur J Cancer 1997; 33:2216-20. [PMID: 9470809 DOI: 10.1016/s0959-8049(97)00318-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The concentration of total sialic acid (TSA) is increased in the plasma of patients with many types of cancer. The purpose of this study was to assess the usefulness of the TSA marker in predicting the efficacy of the treatment, and to compare TSA with two common markers, carcinoembryonic antigen (CEA) and the carbohydrate antigen 19-9 (CA 19-9). The study was performed on 44 patients treated for advanced colorectal carcinoma by a weekly 8 h continuous infusion of 5-fluorouracil (1300 mg/m2) plus bolus injection of L-folinic acid (100 mg/m2). TSA, CEA and CA 19-9 levels were measured before and after 3 months of treatment and their variations analysed as a function of the response to the treatment. TSA levels of patients with metastatic colorectal carcinoma before treatment (959 +/- 265 mg/l) were significantly higher than those of 32 healthy people (584 +/- 99 mg/l). The percentage of patients with TSA concentration above the cut-off level (782 mg/l) was 73% before treatment and 23% after. All patients who experienced an objective response to the treatment (complete, partial or minor response) (n = 29) had a significant decrease of TSA levels (t = 5.96; P < 0.001). When the disease was considered as stabilised (n = 10), TSA changed slightly, but it increased with progressive disease (4 out of 5 patients). Changes in CEA and CA 19-9 did not correlate as well as TSA to the treatment efficacy. Initial levels of TSA did not permit prediction of the efficacy of the treatment since they were not significantly different between the five response groups. TSA seems to be more likely involved in tumour changes than in tumour volume. Its determination could provide useful information about the spreading and metastatic properties of the tumour. TSA normalisation is an indicator of probable tumour growth arrest and its elevation could be a marker of relapse.
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Affiliation(s)
- T Painbeni
- Laboratoire de Pharmacologie et Toxicologie, CHU Angers, France
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Abstract
OBJECTIVE Serum sialic acid has recently gained interest as a possible cardiovascular risk factor as well as a potential tumour marker. The effect of pregnancy on serum sialic acid is unclear particularly in the post-partum period. DESIGN Longitudinal cohort. SETTING Teaching hospital antenatal clinic. POPULATION 29 pregnant women, 27 age matched non-pregnant women. METHODS Specific enzymatic assay for sialic acid. The first serum sample was taken between 37 and 42 weeks of gestation; in 22 women this was followed by a second serum sample at 12 weeks postpartum. Serum sialic acid concentration was also measured in the 27 controls. RESULTS Mean (SD) serum sialic acid concentration was higher during pregnancy than post-partum: 91.1 (11.1) v 77.5 (11.1) mg/dl (p < 0.001); or in the control group: 66.0 (9.7) mg/dl (p < 0.001). CONCLUSIONS Serum sialic acid is elevated during pregnancy and postpartum.
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Affiliation(s)
- M Crook
- Department of Chemical Pathology, Guy's and St Thomas' Hospital, London, UK
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Feijoo C, Páez de la Cadena M, Rodríguez-Berrocal FJ, Martínez-Zorzano VS. Sialic acid levels in serum and tissue from colorectal cancer patients. Cancer Lett 1997; 112:155-60. [PMID: 9066722 DOI: 10.1016/s0304-3835(96)04564-8] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Sialic acid levels were determined in serum and in both normal and tumour-derived tissues from 30 patients with colorectal cancer. Total sialic acid (TSA), bound sialic acid (BSA),TSA normalised to total protein (TSA/TP) and BSA normalised to total protein (BSA/TP) were significantly higher (P < 0.0001) in sera from patients than in normal subjects. We found a trend of increasing serum sialic acid levels (TSA/TP and BSA/TP) as the malignancy became more severe (i.e. Dukes' stages A to C). Comparison of sialic acid levels between normal and tumour-derived colorectal tissues indicated no statistically significant differences in TSA, BSA or FSA (free sialic acid) levels between both tissues; however, TSA/TP and BSA/TP values were significantly decreased (P < 0.05) in the tumoral tissue. In this study, the possible relation between serum and tumour sialic acid levels in colorectal cancer patients was investigated. Our results showed that in these patients there was no correlation between serum BSA and tumour BSA levels.
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Affiliation(s)
- C Feijoo
- Department of Fundamental Biology, University of Vigo, Spain
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Crook MA, Treloar A, Haq M, Tutt P. Serum total sialic acid and acute phase proteins in elderly subjects. EUROPEAN JOURNAL OF CLINICAL CHEMISTRY AND CLINICAL BIOCHEMISTRY : JOURNAL OF THE FORUM OF EUROPEAN CLINICAL CHEMISTRY SOCIETIES 1994; 32:745-7. [PMID: 7532440 DOI: 10.1515/cclm.1994.32.10.745] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Serum total sialic acid has gained recent interest as a cardiovascular risk factor. We measured serum total sialic acid and three acute phase proteins; C-reactive protein, alpha 1-antichymotrypsin and alpha 1-acid glycoprotein in 37 geriatric patients (age 80.1 +/- 7.0 years) and 50 younger subjects (age 40.3 +/- 11.4 years). Serum total sialic acid was higher in the geriatric subjects 2.41 +/- 0.39 mmol/l versus 2.04 +/- 0.35 mmol/l, P < 0.04. Serum alpha 1-acid glycoprotein, alpha 1-antichymotrypsin and C-reactive protein were also elevated in the geriatric patients; serum alpha 1-acid glycoprotein being 1.16 +/- 0.32 g/l versus 0.41 +/- 0.28 g/l, P < 0.0001, serum alpha 1-antichymotrypsin being 0.80 +/- 0.20 g/l versus 0.52 +/- 0.10 g/l, P < 0.0001 and serum C-reactive protein being 9.71 +/- 21.0 mg/l versus 4.73 +/- 1.30 mg/l, P < 0.04. There was a correlation with serum total sialic acid and serum alpha 1-acid glycoprotein and alpha 1-antichymotrypsin in the geriatric subjects and with alpha 1-acid glycoprotein, alpha 1-antichymotrypsin and C-reactive protein in the younger group.
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Affiliation(s)
- M A Crook
- Department of Clinical Chemistry, Guy's Hospital, London, England, U.K
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Thougaard AV, Jensen AL, Wenck A. Evaluation of an automated spectrophotometric assay for the determination of total sialic acid in canine serum. Vet Res Commun 1994; 18:337-45. [PMID: 7863605 DOI: 10.1007/bf01839284] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
This study validates an automated enzymatic assay using the Cobas Fara (Roche) centrifugal analyser, which offers a reliable measurement of the total sialic acid concentration in canine serum as assessed by evaluating the precision and accuracy. Data are presented on the biological variation in the total serum sialic acid concentration. Measurements of total serum sialic acid concentration appear to be useful in distinguishing dogs with neoplastic disorders from clinically healthy dogs.
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Affiliation(s)
- A V Thougaard
- Central Laboratory, Royal Veterinary and Agricultural University, Frederiksberg, Denmark
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Hrzenjak T, Roguljić A, Kasuba V, Karlović M. The role of sialic acid and Ca2+ ions in rabies virus-infected foxes brain. Comp Immunol Microbiol Infect Dis 1994; 17:71-5. [PMID: 8004936 DOI: 10.1016/0147-9571(94)90008-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
The receptors for rabies virus on the neuron membranes are polysialogangliosides arranged in multicomponent gelate structures. The impulse conductivity at the synapse membranes also depends on the interactions between negatively charged sialic acid from the oligosaccharide parts of gangliosides and positively charged Ca ions. From individual brain regions of healthy foxes and foxes naturally infected with rabies virus glycolipoprotein preparations were isolated. In them, the presence of polysialogangliosides and the concentration of sialic acid, Ca ions, and proteins were evidenced. The concentration of sialic acid was increased in all tested brain regions of the infected foxes. In the preparations from the cortex cerebri or cornu Ammonis of the infected foxes, 20-fold higher levels of sialic acid and the decreased concentrations of Ca ions were recorded. The increase in sialic acid levels is directly responsible for the augmented negative charge at synaptic membranes and, consequently, for a much higher permeability of these membranes, which results in a persistent stimulation followed by the release of neuro-transmitters.
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Affiliation(s)
- T Hrzenjak
- Department of Biology, Faculty of Veterinary Medicine, Zagreb, Croatia
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