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Sample records for antigens tumor-associated carbohydrate

  1. Ultrasensitive photoelectrochemical immunoassay of antibody against tumor-associated carbohydrate antigen amplified by functionalized graphene derivates and enzymatic biocatalytic precipitation.

    Science.gov (United States)

    Zhang, Xiaoru; Liu, Mingshuai; Mao, Yaning; Xu, Yunpeng; Niu, Shuyan

    2014-09-15

    Tumor-associated carbohydrate antigens (TACAs) are often found on the surface of cancer cells. The determination of the carbohydrate components of glycoconjugates is challenging because of the chemical complexity of glycan chains. Through monitoring corresponding antibody, we can get a good solution for clinical diagnosis. Here breast tumor-associated carbohydrate antigens Tn were used as a model and a new photoelectrochemical biosensor for ultrasensitive detection of antibody against Tn was developed. To enhance the sensitivity, both graphene oxide and graphene were used during the construction of biosensor. Through the formation of immunocomplex and the insoluble biocatalytic precipitation (BCP) product, photocurrent intensity was decreased greatly and the antibody could be detected from 0.5 to 500 pg/mL with a detection limit of 1.0×10(-13) g/mL. At the same time, the developed biosensor showed acceptable selectivity and could be used in the complex matrix. Compared with the traditional glycoarray method, this PEC method is more sensitive (5 orders of magnitude), and thus provides another platform to monitor the immune response to carbohydrate epitopes at different stages during differentiation, metastasis, or treatment.

  2. Valency and density matter: Deciphering impacts of immunogen structures on immune responses against a tumor associated carbohydrate antigen using synthetic glycopolymers.

    Science.gov (United States)

    Qin, Qian; Yin, Zhaojun; Wu, Xuanjun; Haas, Karen M; Huang, Xuefei

    2016-09-01

    For successful carbohydrate based anti-cancer vaccines, it is critical that B cells are activated to secret antibodies targeting the tumor associated carbohydrate antigens (TACAs). Despite the availability of many TACA based constructs, systematic understanding of the effects of structural features on anti-glycan antibody responses is lacking. In this study, a series of defined synthetic glyco-polymers bearing a representative TACA, i.e., the Thomsen-nouveau (Tn) antigen, have been prepared to probe the induction of early B cell activation and antibody production via a T cell independent mechanism. Valency and density of the antigen in the polymers turned out to be critical. An average of greater than 6 Tn per chain was needed to induce antibody production. Glycopolymers with 40 antigens per chain and backbone molecular weight of 450 kDa gave the strongest stimulation to B cells in vitro, which correlated well with its in vivo activity. Deviations from the desired valency and density led to decreased antibody production or even antigen specific B cell non-responsiveness. These findings provide important insights on how to modulate anti-TACA immune responses facilitating the development of TACA based anti-cancer vaccines using glycopolymers. PMID:27294537

  3. Enhancing the recognition of tumor associated antigens

    OpenAIRE

    Restifo, Nicholas P; Irvine, Kari R.; Minev, Boris R.; Taggarse, Akash S.; McFariand, Barbra J.; Wang, Michael

    1994-01-01

    Activated CD8+ T cells (TCD8+) can directly recognize malignant cells because processed fragments of tumor associated antigens (TAA), 8-10 amino acids in length and complexed with MHC class I molecules, are displayed on tumor cell surfaces. Tumor cells have been genetically modified in a variety of ways in efforts to enhance the immune recognition of TAA. An alternative strategy is the expression of TAA in recombinant or synthetic form. This has been made possible by the recent cloning of TAA...

  4. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kiessling, Andrea [Biologics Safety and Disposition, Preclinical Safety, Translational Sciences, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Werk Klybeck, Klybeckstraße 141, Basel CH-4057 (Switzerland); Wehner, Rebekka [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Füssel, Susanne [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Bachmann, Michael [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Wirth, Manfred P. [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Schmitz, Marc, E-mail: marc.schmitz@tu-dresden.de [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany)

    2012-02-22

    Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8{sup +} cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4{sup +} T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy.

  5. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    International Nuclear Information System (INIS)

    Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8+ cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4+ T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy

  6. Targeting of tumor-associated antigens (TAA) in experimental immunotherapy

    International Nuclear Information System (INIS)

    We have previously shown the superiority of tumor-associated antigens (TAA) to function as effective immunogens when administered with bilayer membrane vesicles called liposomes. The ability of liposomes to target TAA to host antigen-presenting cells is analyzed here. 1-Butanol extracted TAA from two syngeneic rat colon cancer tumors (WB 2054 and W 1756) was radioiodinated (131I-TAA). Free 131I and 131I-TAA (2.8 X 10(7) cpm and 75 micrograms TAA per rat) were used as tracers, with or without incorporation into liposomes (composition: sphingomyelin, cholesterol, dicetyl phosphate at 70:24:6 molar ratio). Six groups of male rats (BN X WF for WB2054 and Wistar/Furth for W1756, n = 18 each group) were injected iv with either free tracers or the tracers incorporated into liposomes. Whole blood clearance curve was biphasic (half-life alpha = 5 min; half life beta = 12 hr), suggesting a two-compartmental model of distribution. Seven animals from each group were sacrificed at set times (15 min to 48 hr), organs harvested and cpm/g of tissue estimated. Liposome 131I and liposome 131I-TAA were targeted to and retained preferentially in liver and spleen. Four animals from each group were imaged serially using a gamma camera. Matched pair analysis of regions showed persistently higher activity in liver-spleen area when liposomes were used (P less than 0.001). The uptake of radiolabeled antigens by plastic adherent mononuclear cells in liver and spleen was significantly higher when presented with liposomes (macrophage uptake index: liver = 1.65 vs 0.55; spleen = 5.85 vs 1.15; with and without liposomes, respectively)

  7. MYCN: From Oncoprotein To Tumor-Associated Antigen

    Directory of Open Access Journals (Sweden)

    Vito ePistoia

    2012-11-01

    Full Text Available MYCN is a well known oncogene overexpressed in different human malignancies including neuroblastoma, rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms’ tumor and small cell lung cancer. In the case of neuroblastoma (NB, MYCN amplification is an established biomarker of poor prognosis. MYCN belongs to a family of transcription factors (the most important of which is CMYC that show a high degree of homology. Downregulation of MYC protein expression leads to tumor regression in animal models, indicating that MYC proteins represent interesting therapeutic targets.Pre-requisites for a candidate tumor-associated antigen (TAA to be targeted by immunotherapeutic approaches are the following, i expression should be tumor-restricted, ii the putative TAA should be up-regulated in cancer cells and iii protein should be processed into immunogenic peptides capable of associating to MHC molecules with high affinity. Indeed, the MYCN protein is not expressed in human adult tissues and upregulated variably in NB cells, and MYCN peptides capable of associating to HLA-A1 or –A2 molecules with high affinity have been identified. Thus the MYCN protein qualifies as putative TAA in NB.Additional issues that determine the feasibility of targeting a putative TAA with cytotoxic T lymphocytes (CTL and will be here discussed are the following, i the inadequacy of tumor cells per se to act as antigen-presenting cells witnessed, in the case of NB cells, by the low to absent expression of HLA- class I molecules, the lack of costimulatory molecules and multiple defects in the HLA class I related antigen processing machinery, and ii the immune evasion mechanisms operated by cancer cells to fool the host immune system, such as up-regulation of soluble immunosuppressive molecules (e.g. soluble MICA and HLA-G in the case of NB or generation of immunosuppressive cells in the tumor microenvironment. A final issue that deserves consideration is the strategy used to generate

  8. New tumor-associated antigen SC6 in pancreatic cancer

    OpenAIRE

    Liu, Min-Pei; Guo, Xiao-Zhong; Xu, Jian-Hua; Wang, Di; Li, Hong-Yu; Cui, Zhong-Min; Zhao, Jia-Jun; Ren, Li-Nan

    2005-01-01

    AIM: To examine the concentration of a new antigen SC6 (SC6-Ag) recognized by monoclonal antibody (MAb) in patients with pancreatic cancer and other malignant or benign diseases and to understand whether SC6-Ag has any clinical significance in distinguishing pancreatic cancer from other gastrointestinal diseases.

  9. New tumor-associated antigen SC6 in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Min-Pei Liu; Xiao-Zhong Guo; Jian-Hua Xu; Di Wang; Hong-Yu Li; Zhong-Min Cui; Jia-Jun Zhao; Li-Nan Ren

    2005-01-01

    AIM: To examine the concentration of a new antigen SC6 (SC6-Ag) recognized by monoclonal antibody (MAb)in patients with pancreatic cancer and other malignant or benign diseases and to understand whether SC6-Ag has any clinical significance in distinguishing pancreatic cancer from other gastrointestinal diseases.METHODS: Six hundred and ninety-five serum specimens obtained from 115 patients with pancreatic cancer, 154 patients with digestive cancer and 95patients with non-digestive cancer were used and classified in this study. Serum specimens obtained from 140 patients with benign digestive disease and 89 patients with non-benign digestive disease served as controls. Ascites was tapped from 16 pancreatic cancer patients, 19 hepatic cancer patients, 16 colonic cancer patients, 10 gastric cancer and 6 severe necrotic pancreatitis patients. The samples were quantitated by solid-phase radioimmunoassay. The cut-off values (CV)of 41, 80, and 118 U/mL were used.RESULTS: The average intra- and interassay CV detected by immunoradiometric assay of SC6-Ag was 5.4% and 8.7%, respectively. The sensitivity and specificity were 73.0% and 90.9% respectively. The levels in most malignant and benign cases were within the normal upper limit. Among the 16 pancreatic cancer cases, the concentration of SC6-Ag in ascites was over the normal range in 93.8% patients. There was no significant difference in the concentration of SC6-Ag.Decreased expression of SC6-Ag in sera was significantly related to tumor differentiation. The concentration of SC6-Ag was higher in patients before surgery than after surgery. The specificity of SC6-Ag and CA19-9 was significantly higher than that of ultrasound and computer tomography (CT) in pancreatic cancer patients. Higher positive predictive values were indicated in 92.3% SC6-Ag and 88.5% CA19-9, but lower in 73.8% ultrasound and 76.2% CT.CONCLUSION: The combined test of SC6-Ag and CA19-9 may improve the diagnostic rate of primary cancer. The detection of

  10. HCA520, A NOVEL TUMOR ASSOCIATED ANTIGEN, INVOLVED IN CELL PROLIFERATION AND APOPTOSIS

    Institute of Scientific and Technical Information of China (English)

    杨美香; 曲迅; 刘福利; 郑广娟

    2003-01-01

    Objective: Tumor associated antigen encoding gene HCA520 (AF146019) was identified by screening a human hepatocellular carcinoma expressing cDNA library using SEREX technique. In this experiment we studied the effect of HCA520 on cell proliferation and apoptosis. Methods: Gene HCA520 was gained by PCR and transfected into 293 cells. The stable expression cells were obtained by G418 selection. The cell proliferation was measured by [3H]-TdR uptake and apoptosis assay was measured by FACS. Results: Eukaryotic expression plasmid pcDNA3-HCA520 was constructed and its stable transfectants were obtained. Overexpression of HCA520 inhibited the cell proliferation and enhanced cell apoptosis after serum deprivation. Conclusion: HCA520 is a novel tumor associated antigen that can affect cell proliferation and apoptosis.

  11. Identification of tumor-associated antigens as diagnostic and predictive biomarkers in cancer.

    Science.gov (United States)

    Zhang, Jian-Ying; Looi, Kok Sun; Tan, Eng M

    2009-01-01

    Many studies demonstrated that cancer sera contain antibodies which react with autologous cellular antigens generally known as tumor-associated antigens (TAAs). In our laboratories, the approach used in the identification of TAAs has involved initially examining the sera of cancer patients using extracts of tissue culture cells as source of antigens in Western blotting and by indirect immunofluorescence on whole cells. With these two techniques, we identify sera which have high-titer fluorescent staining or strong signals to cell extracts on Western blotting and subsequently use these sera as probes in immunoscreening cDNA expression libraries, and also in proteomic approaches to isolate and identify targeted antigens which might potentially be involved in malignant transformation. In this manner, several novel TAAs including HCC1, p62, p90, and others have been identified. In extension of these studies, we evaluate the sensitivity and specificity of different antigen-antibody systems as markers in cancer in order to develop "tumor-associated antigen array" systems for cancer diagnosis, cancer prediction, and for following the response of patients to treatment. PMID:19381943

  12. Human lung tumor-associated antigen identified as an extracellular matrix adhesion molecule

    OpenAIRE

    1991-01-01

    A single chain glycoprotein with an estimated molecular mass of 160 kD (gp160) was previously identified as a human lung tumor-associated antigen. This tumor marker is shown here to be associated noncovalently with a second 130-kD protein. Sequential immunoprecipitation studies of surface iodinated lung tumor cell lysates reveal that this heterodimeric complex is indistinguishable serologically and structurally from the integrin VLA-2, found originally on activated T lymphocytes and platelets...

  13. 78 FR 11895 - Prospective Grant of Exclusive License: Development of MUC-1 Tumor Associated Antigens as Cancer...

    Science.gov (United States)

    2013-02-20

    ...-1 Tumor Associated Antigens as Cancer Vaccines for Bladder Cancer, Breast Cancer, Colorectal Cancer, Gastric Cancer, Kidney Cancer, Liver Cancer, Lung Cancer, Ovarian Cancer, Prostate Cancer and Pancreatic..., gastric cancer, kidney cancer, liver cancer, lung cancer, ovarian......

  14. Microvesicle Cargo of Tumor-Associated MUC1 to Dendritic Cells Allows Cross-presentation and Specific Carbohydrate Processing

    DEFF Research Database (Denmark)

    Rughetti, Aurelia; Rahimi, Hassan; Belleudi, Francesca;

    2014-01-01

    Tumor-associated glycoproteins are a group of antigens with high immunogenic interest: The glycoforms generated by the aberrant glycosylation are tumor-specific and the novel glycoepitopes exposed can be targets of tumor-specific immune responses. The MUC1 antigen is one of the most relevant tumo...... for the design of glycoprotein-based immunogens for cancer immunotherapy. Cancer Immunol Res; 2(2); 177-86. ©2013 AACR....

  15. Tumor associated antigen specific T-cell populations identified in ex vivo expanded TIL cultures

    DEFF Research Database (Denmark)

    Junker, Niels; Kvistborg, Pia; Køllgaard, Tania;

    2012-01-01

    Ex vivo expanded tumor infiltrating lymphocytes (TILs) from malignant melanoma (MM) and head & neck squamous cell carcinoma (HNSCC) share a similar oligoclonal composition of T effector memory cells, with HLA class I restricted lysis of tumor cell lines. In this study we show that ex vivo expanded...... TILs from MM and HNSCC demonstrate a heterogeneous composition in frequency and magnitude of tumor associated antigen specific populations by Elispot IFN¿ quantitation. TILs from MM and HNSCC shared reactivity towards NY ESO-1, cyclin B1 and Bcl-x derived peptides. Additionally we show that dominating...... the heterogeneous tumors upon adoptive transfer; increasing the probability of tumor control by minimizing immune evasion by tumor cell escape variants....

  16. Targeting tumor-associated antigens to the MHC class I presentation pathway.

    Science.gov (United States)

    Gross, G; Margalit, A

    2007-06-01

    There is little doubt that cytotoxic T lymphocytes (CTLs) can kill tumor cells in-vivo. However, most CTL-inducing immunization protocols examined so far in cancer patients have yielded only limited clinical benefits, underscoring the urge to improve current approaches for the effective induction of tumor-reactive CTLs. The tumor side of the immunological frontline is armed with large masses, high mutability and an arsenal of immune evasion and suppression mechanisms. Accordingly, the confronting CTLs should come in large numbers, recognize an assortment of MHC class I (MHC-I) bound tumor-associated peptides and be brought into action under effective immunostimulatory conditions. Naïve CTLs are activated to become effector cells in secondary lymphoid organs, following their productive encounter with MHC-I-bound peptides at the surface of dendritic cells (DCs). Therefore, many cancer vaccines under development focus on the optimization of peptide presentation by DCs at this critical stage. The elucidation of discrete steps and the subsequent identification of inherent bottlenecks in the MHC-I antigen presentation pathway have fueled elaborate efforts to enhance vaccine efficacy by the rational targeting of proteins or peptides, formulated into these vaccines, to this pathway. Protein- and gene-based strategies are accordingly devised to deliver tumor-associated peptides to selected cellular compartments, which are essential for the generation of functional CTL ligands. Many of these strategies target the conventional, endogenous route, while others harness the unique pathways that enable DCs to present exogenous antigens, known as cross-presentation. Here we dissect the intricate machinery that produces CTL ligands and examine how knowledge-based cancer vaccines can target the sequence of workstations, biochemical utensils and molecular intermediates comprising this production line.

  17. Targeting tumor-associated antigens to the MHC class I presentation pathway.

    Science.gov (United States)

    Gross, G; Margalit, A

    2007-06-01

    There is little doubt that cytotoxic T lymphocytes (CTLs) can kill tumor cells in-vivo. However, most CTL-inducing immunization protocols examined so far in cancer patients have yielded only limited clinical benefits, underscoring the urge to improve current approaches for the effective induction of tumor-reactive CTLs. The tumor side of the immunological frontline is armed with large masses, high mutability and an arsenal of immune evasion and suppression mechanisms. Accordingly, the confronting CTLs should come in large numbers, recognize an assortment of MHC class I (MHC-I) bound tumor-associated peptides and be brought into action under effective immunostimulatory conditions. Naïve CTLs are activated to become effector cells in secondary lymphoid organs, following their productive encounter with MHC-I-bound peptides at the surface of dendritic cells (DCs). Therefore, many cancer vaccines under development focus on the optimization of peptide presentation by DCs at this critical stage. The elucidation of discrete steps and the subsequent identification of inherent bottlenecks in the MHC-I antigen presentation pathway have fueled elaborate efforts to enhance vaccine efficacy by the rational targeting of proteins or peptides, formulated into these vaccines, to this pathway. Protein- and gene-based strategies are accordingly devised to deliver tumor-associated peptides to selected cellular compartments, which are essential for the generation of functional CTL ligands. Many of these strategies target the conventional, endogenous route, while others harness the unique pathways that enable DCs to present exogenous antigens, known as cross-presentation. Here we dissect the intricate machinery that produces CTL ligands and examine how knowledge-based cancer vaccines can target the sequence of workstations, biochemical utensils and molecular intermediates comprising this production line. PMID:17584150

  18. Role of tumor-associated antigen expression in radioimmunoguided surgery for colorectal and breast cancer.

    Science.gov (United States)

    Bertoglio, S; Percivale, P; Schenone, F; Peressini, A; Murolo, C; Badellino, F

    1998-12-01

    One hundred thirty-six patients with colorectal and breast cancer were enrolled in a retrospective study using radioimmunoguided surgery (RIGS) with Iodine-125 (I125) radiolabeled B72.3 (Group A, 73 patients) and F023C5 (Group B, 63 patients) monoclonal antibodies (MAbs). The correlation between intraoperative tumor-to-normal tissue (T/NT) gamma-detecting probe (GDP) counts ratio and the expression of tumor-associated glycoprotein (TAG)-72 (GroupA patients) and carcinoembryonic antigen (CEA; Group B patients) tumor-associated antigens (TAA) expression of 209 resected or biopsy tumor specimens was assessed. Ex vivo radioimmunolocalization index (R.I.) was carried out on the same specimens as a control of intraoperative GDP ratio values. RIGS positive definition of tumor occurred in 80/113 (70.8%) tumor sites of Group A patients and in 84/96 (87.5%) tumor sites of Group B patients. Mean percent B72.3 TAA expression of 113 tumor sites of Group A patients was 62.74 +/- 28.79% vs. 73.00 +/- 26.28% of 96 tumor sites of Group B patients (P < 0.05). The higher incidence of positive RIGS results was observed in tumor sites with the higher expression of the relative TAA. A statistically significant correlation between RIGS ratios and B72.3 and CEA expression was observed in the 113 tumor sites of Group A (P < 0.05) and in the 96 tumor sites of Group B (P < 0.01), respectively. The role of a preoperative evaluation of TAA expression in patients undergoing RIGS is discussed. Its assessment, whenever possible, may help to select those patients who will benefit more from this immunodiagnostic technique.

  19. Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers.

    Science.gov (United States)

    Wernicke, Alla Gabriella; Varma, Sonal; Greenwood, Eleni A; Christos, Paul J; Chao, K S Clifford; Liu, He; Bander, Neil H; Shin, Sandra J

    2014-06-01

    Prostate-specific membrane antigen (PSMA) has been found to be expressed in the tumor-associated neovasculature of multiple solid tumor types including breast cancers. However, thus far, the number of cases studied from some tumor types has been limited. In this study, we set out to assess PSMA expression in the tumor-associated vasculature associated with invasive breast carcinomas in a sizable cohort of patients. One hundred and six patients with AJCC stage 0-IV breast cancer were identified. Ninety-two of these patients had primary breast cancer [invasive breast carcinoma with or without co-existing ductal carcinoma in situ (DCIS) (74) or DCIS alone (18)]. In addition, 14 patients with breast cancer metastases to the brain were identified. Immunohistochemical staining for PSMA and CD31 was performed on parallel representative tumor sections in each case. Tumor-associated vascular endothelial cell PSMA immunoreactivity was semi-quantitatively assessed based on two parameters: overall percent of endothelial positivity and staining intensity. PSMA expression for tumor-associated vascular endothelial cells was scored 0 if there was no detectable PSMA expression, 1 if PSMA staining was detectable in 5-50%, and 2 if PSMA expression was positive in >50% of microvessels. CD 31 staining was concurrently reviewed to confirm the presence of vasculature in each case. Tumor-associated vasculature was PSMA-positive in 68/92 (74%) of primary breast cancers and in 14/14 (100%) of breast cancers metastatic to brain. PSMA was not detected in normal breast tissue or carcinoma cells. All but 2 cases (98%) showed absence of PSMA expression in normal breast tissue-associated vasculature. The 10-year overall survival was 88.7% (95% CI = 80.0%, 93.8%) in patients without brain metastases. When overall survival (OS) was stratified based on PSMA score group, patients with PSMA scores of 0, 1, and 2 had 10-year OS of 95.8%, 96.0%, and 79.7%, respectively (p = 0.12). When PSMA scores

  20. T-cell response to p53 tumor-associated antigen in patients with colorectal carcinoma.

    Science.gov (United States)

    Bueter, Marco; Gasser, Martin; Schramm, Nicolai; Lebedeva, Tatiana; Tocco, Georges; Gerstlauer, Christiane; Grimm, Martin; Nichiporuk, Ekaterina; Thalheimer, Andreas; Thiede, Arnulf; Meyer, Detlef; Benichou, Gilles; Waaga-Gasser, Ana Maria

    2006-02-01

    Despite the radical surgical resection performed in patients with colorectal carcinoma, there is a high rate of tumor recurrence. Over an observation period of 3 years, 18% of the patients in our collective suffered a tumor relapse with local or distinct metastases after initial R0-resection. Some evidence suggests that this may be due to suppression of anti-tumor responses, a phenomenon that might be attributed to regulatory T cells. The aim of our study was to investigate the tumor-specific immune response depending on the UICC stage of patients with colorectal cancer. The cellular immune responses against defined antigens that are overexpressed in most of the patients with colorectal cancer were characterized. For this purpose, the tumor suppressor gene, p53, was chosen as the tumor-associated antigen that exhibits mutations and overexpression in up to 60% of colorectal carcinoma. We observed that p53 induced both IFN-gamma and IL-10 secretion. The predominance of IL-10 production indicated that regulatory T cells directly participate in modulating the anti-tumor immune response. IL-10 levels in the blood as well as the expression of regulatory T-cell specific genes at the tumor site correlate with the UICC stage of the disease. These results may provide an explanation for the poor prognosis and increased recurrence rate in patients with advanced carcinoma.

  1. Novel Tumor-associated Antigen of Hepatocellular Carcinoma Defined by Monoclonal Antibody E4-65

    Institute of Scientific and Technical Information of China (English)

    Ke ZOU; Jihang JU; Hong XIE

    2007-01-01

    A monoclonal antibody, E4-65, produced by immunizing mice with SMMC-7721 cells, a human hepatocellular carcinoma (HCC) cell line, was used to identify and characterize an unreported HCC-associated antigen. Indirect immunofluorescence studies showed that E4-65 antibody reacted with five out of eight HCC cell lines, but not with 10 non-HCC tumor cell lines or a normal liver cell line. Using immunohistochemical examination, E4-65 antigen was detected on the cell membranes and in the cytoplasm of human liver tumor tissues, but was not found in most other tumors, or normal adult or fetal tissues, except for a weakly positive reaction in tissues of the digestive system. Western blot analysis showed that E4-65 antibody bound to a 45 kDa protein in the human HCC cell line and tissue lysates. Enzyme treatment and lectin blotting did not detect the carbohydrate chain in E4-65 antigen. This HCC-associated protein represents a potentially useful target for diagnoses and immunotherapy of human HCC.

  2. Autoantibodies to Tailor-Made Panels of Tumor-Associated Antigens in Breast Carcinoma

    Directory of Open Access Journals (Sweden)

    Ettie Piura

    2011-01-01

    Full Text Available Autoantibodies (AAbs to tumor-associated antigens (TAAs have been identified in the sera of cancer patients. In a previous review published in this journal, we have focused on recent knowledge related to circulating AAbs to individual TAAs in breast carcinoma. This review will focus on recent knowledge related to AAb assays to tailor-made panels of TAAs in breast carcinoma. So far, AAb assays to the following tailor-made panels of TAAs have been assessed in breast carcinoma: (1 p53, c-myc, HER2, NY-ESO-1, BRCA2, and MUC1, (2 IMP1, p62, Koc, p53, c-MYC, cyclin B1, and survivin, (3 PPIA, PRDX2, FKBP52, HSP-60, and MUC1, (4 MUC1, HER2, p53, and IGFBP2, (5 p53, HER2, IGFBP-2, and TOPO2α, (6 survivin and livin, (7 ASB-9, SERAC1, and RELT, and (8 p16, p53, and c-myc. Assessment of serum AAbs to a tailor-made panel of TAAs provides better sensitivity to diagnosis of breast carcinoma than measuring serum AAbs to a single TAA. Nevertheless, measurement of serum AAbs to a panel of TAAs for screening and early diagnosis of breast carcinoma is still investigational and should be carried out along with traditional diagnostic studies.

  3. Identification of a New Member of the Ep-CAM (17-1A)Tumor-Associated Antigen Family

    Institute of Scientific and Technical Information of China (English)

    秦莉; 陈应华

    2002-01-01

    The tumor-associated antigen Ep-CAM (17-1A antigen), defined by the murine monoclonal antibody (mAb) 17-1A, has been identified as a 42-kD glycoprotein. The mAb 17-1A has been used for immunotherapy of colorectal cancer. We obtained mAb 19F4 using a synthetic peptide containing antigen determinants of 17-1A antigen. The mAb 19F4 can bind the corresponding dominants of the 17-1A antigen in ELISA. Western-blot analysis demonstrated that mAb 19F4 recognized a 50-kD protein from cell lysates of MCF-7 (breast cancer cell line). Both mAb 19F4 and 17-1A detected a 42-kD protein in the cell lysates of HT-29 (colorectal cancer cell line). The results suggest that new members of the tumor-associated antigen family 17-1A may exist.

  4. Tumor-associated antigens identified by mRNA expression profiling induce protective anti-tumor immunity

    DEFF Research Database (Denmark)

    Mathiassen, Søren; Lauemøller, S L; Ruhwald, Morten;

    2001-01-01

    Defined tumor-associated antigens (TAA) are attractive targets for anti-tumor immunotherapy. Here, we describe a novel genome-wide approach to identify multiple TAA from any given tumor. A panel of transplantable thymomas was established from an inbred p53-/- mouse strain. The resulting tumors were...... imprints, which may be used to identify patient-specific arrays of TAA. This may enable a multi-epitope based immunotherapy with improved prospects of clinical tumor rejection....

  5. Molecular cloning of cDNA for the human tumor-associated antigen CO-029 and identification of related transmembrane antigens

    Energy Technology Data Exchange (ETDEWEB)

    Szala, S.; Kasai, Yasushi; Steplewski, Z.; Rodeck, U.; Koprowski, H.; Linnenbach, A.J. (Wistar Inst. of Anatomy and Biology, Philadelphia, PA (USA))

    1990-09-01

    The human tumor-associated antigen CO-029 is a monoclonal antibody-defined cell surface glycoprotein of 27-34 kDa. By using the high-efficiency COS cell expression system, a full-length cDNA clone for CO-029 was isolated. When transiently expressed in COS cells, the cDNA clone directed the synthesis of an antigen reactive to monoclonal antibody CO-029 in mixed hemadsorption and immunoblot assays. Sequence analysis revealed that CO-029 belongs to a family of cell surface antigens that includes the melanoma-associated antigen ME491, the leukocyte cell surface antigen CD37, and the Sm23 antigen of the parasitic helminth Schistosoma mansoni. CO-029 and ME491 antigen expression and the effect of their corresponding monoclonal antibodies on cell growth were compared in human tumor cell lines of various histologic origins.

  6. Development of oligoclonal nanobodies for targeting the tumor-associated glycoprotein 72 antigen

    DEFF Research Database (Denmark)

    Sharifzadeh, Zahra; Rahbarizadeh, Fatemeh; Shokrgozar, Mohammad Ali;

    2013-01-01

    The tumor-associated glycoprotein 72 (TAG-72) is a membrane mucin whose over-expression is correlated with advanced tumor stage and increased invasion and metastasis. In this study, we identified a panel of four nanobodies, single variable domains of dromedary heavy-chain antibodies that specific...

  7. Development of a double-antibody radioimmunoassay for detecting ovarian tumor-associated antigen fraction OCA in plasma

    International Nuclear Information System (INIS)

    Ovarian tumor-associated antigen isolated from human tumor tissue was shown to have a different mobility from that of carcinoembryonic antigen (CEA) in both acrylamide gel electrophoresis and immunoelectrophoresis in agarose. The ovarian tumor antigen is composed of six species with different electrophoretic mobility in acrylamide gel electrophoresis. Three of these species were detected in Sephadex G-100 ovarian fraction OCA (from the void volume peak) and the other three species of lower apparent molecular weight were detected in fraction OCD (from the second peak). Fractions OCA and OCD did not share common antigenic determinants as determined by immunodiffusion. CEA was shown to share antigenic determinants with both OCA and OCD. A double-antibody radioimmunoassay capable of detecting nanogram quantities of plasma OCA was developed. In a preliminary study of ovarian cancer patients, OCA appeared to be a more sensitive marker for ovarian cancer than CEA. There was virtually no correlation (r2 = 0.1) between OCA and CEA levels in these patients, as determined by radioimmunoassay

  8. Cloning and expression of the tumor-associated antigen L6.

    OpenAIRE

    Marken, J S; Schieven, G L; Hellström, I; Hellström, K E; Aruffo, A

    1992-01-01

    The L6 cell surface antigen, which is highly expressed on lung, breast, colon, and ovarian carcinomas, has attracted attention as a therapeutic target for murine monoclonal antibodies and their humanized counterparts. Its molecular nature has, however, remained elusive. Here we describe the expression cloning of a cDNA encoding the L6 antigen. COS cells transfected with this cDNA direct the expression of an approximately 24-kDa surface protein that reacts with the two anti-L6 monoclonal antib...

  9. The anti-apoptotic members of the Bcl-2 family are attractive tumor-associated antigens

    DEFF Research Database (Denmark)

    Straten, Per thor; Andersen, Mads Hald

    2010-01-01

    Anti-apoptotic members of the Bcl-2 family (Bcl-2, Bcl-X(L) and Mcl-2) are pivotal regulators of apoptotic cell death. They are all highly overexpressed in cancers of different origin in which they enhance the survival of the cancer cells. Consequently, they represent prime candidates for anti......, spontaneous cellular immune responses against the Bcl-2 family proteins have been identified as frequent features in cancer patients underscoring that these proteins are natural targets for the immune system. Thus, Bcl-2 family may serve as an important and widely applicable target for anti......-cancer immunotherapeutic strategies, alone or in the combination with conventional therapy. Here, we summarize the current knowledge of Bcl-2 family proteins as T-cell antigens, which has set the stage for the first explorative trial using these antigens in therapeutic vaccinations against cancer, and discuss future...

  10. Mini-Array of Multiple Tumor-Associated Antigens to Enhance Autoantibody Detection for Immunodiagnosis of Hepatocellular Carcinoma

    Science.gov (United States)

    Zhang, Jian-Ying

    2009-01-01

    Liver cancer, especially hepatocellular carcinoma (HCC), is particularly prevalent in Africa and Asia. HCC affects the Hispanic population of the United States at a rate double that of the white population. The majority of people with HCC will die within 1 year of its detection. This high case-fatality rate can in part be attributed to lack of diagnostic methods that allow early detection. How to establish a methodology to identify the high-risk individuals for HCC remains to be investigated. The multi-factorial and multi-step nature in the molecular pathogenesis of human cancers must be taken into account in both the design and interpretation of studies to identify markers which will be useful for early detection of cancer. Our recent studies demonstrated that a mini-array of multiple tumor-associated antigens (TAAs) might enhance autoantibody detection for diagnosis of HCC, especially for the alpha fetoprotein (AFP)-negative cases. It also suggested that different types of cancer might require different panels of TAAs to achieve the sensitivity and specificity required to make immunodiagnosis a feasible adjunct to tumor diagnosis. PMID:17289549

  11. Cancer immunotherapy using novel tumor-associated antigenic peptides identified by genome-wide cDNA microarray analyses.

    Science.gov (United States)

    Nishimura, Yasuharu; Tomita, Yusuke; Yuno, Akira; Yoshitake, Yoshihiro; Shinohara, Masanori

    2015-05-01

    Recent genome-wide cDNA microarray analysis of gene expression profiles in comprehensive tumor types coupled with isolation of cancer tissues by laser-microbeam microdissection have revealed ideal tumor-associated antigens (TAAs) that are frequently overexpressed in various cancers including head and neck squamous cell cancer (HNSCC) and lung cancer, but not in most normal tissues except for testis, placenta, and fetal organs. Preclinical studies using HLA-transgenic mice and human T cells in vitro showed that TAA-derived CTL-epitope short peptides (SPs) are highly immunogenic and induce HLA-A2 or -A24-restricted CTLs. Based on the accumulated evidence, we carried out a phase II clinical trial of the TAA-SP vaccine in advanced 37 HNSCC patients. This study showed a significant induction of TAA-specific CTLs in the majority of patients without serious adverse effects. Importantly, clinical responses including a complete response were observed in this study. Another phase II clinical trial of therapeutic TAA-SP vaccine, designed to evaluate the ability of prevention of recurrence, is ongoing in HNSCC patients who have received curative operations. Further studies in human preclinical studies and in vivo studies using HLA class I transgenic mice showed TAA-derived long peptides (TAA-LPs) have the capacity to induce not only promiscuous HLA class II-restricted CD4(+) T helper type 1 cells but also tumor-specific CTLs through a cross-presentation mechanism. Moreover, we observed an augmentation of TAA-LP-specific T helper type 1 cell responses and tumor antigen-spreading in HNSCC patients vaccinated with TAA-SPs. This accumulated evidence suggests that therapeutic TAA-SPs and LPs vaccines may provide a promising cancer immunotherapy.

  12. Carbohydrate-functionalized nanovaccines preserve HIV-1 antigen stability and activate antigen presenting cells.

    Science.gov (United States)

    Vela Ramirez, J E; Roychoudhury, R; Habte, H H; Cho, M W; Pohl, N L B; Narasimhan, B

    2014-01-01

    The functionalization of polymeric nanoparticles with ligands that target specific receptors on immune cells offers the opportunity to tailor adjuvant properties by conferring pathogen mimicking attributes to the particles. Polyanhydride nanoparticles are promising vaccine adjuvants with desirable characteristics such as immunomodulation, sustained antigen release, activation of antigen presenting cells (APCs), and stabilization of protein antigens. These capabilities can be exploited to design nanovaccines against viral pathogens, such as HIV-1, due to the important role of dendritic cells (DCs) and macrophages in viral spread. In this work, an optimized process was developed for carbohydrate functionalization of HIV-1 antigen-loaded polyanhydride nanoparticles. The carbohydrate-functionalized nanoparticles preserved antigenic properties upon release and also enabled sustained antigen release kinetics. Particle internalization was observed to be chemistry-dependent with positively charged nanoparticles being taken up more efficiently by DCs. Up-regulation of the activation makers CD40 and CD206 was demonstrated with carboxymethyl-α-d-mannopyranosyl-(1,2)-d-mannopyranoside functionalized nanoparticles. The secretion of the cytokines IL-6 and TNF-α was shown to be chemistry-dependent upon stimulation with carbohydrate-functionalized nanoparticles. These results offer important new insights upon the interactions between carbohydrate-functionalized nanoparticles and APCs and provide foundational information for the rational design of targeted nanovaccines against HIV-1. PMID:25068589

  13. Attenuated recombinant vaccinia virus expressing oncofetal antigen (tumor-associated antigen) 5T4 induces active therapy of established tumors.

    Science.gov (United States)

    Mulryan, Kate; Ryan, Matthew G; Myers, Kevin A; Shaw, David; Wang, Who; Kingsman, Susan M; Stern, Peter L; Carroll, Miles W

    2002-10-01

    The human oncofetal antigen 5T4 (h5T4) is a transmembrane glycoprotein overexpressed by a wide spectrum of cancers, including colorectal, ovarian, and gastric, but with a limited normal tissue expression. Such properties make 5T4 an excellent putative target for cancer immunotherapy. The murine homologue of 5T4 (m5T4) has been cloned and characterized, which allows for the evaluation of immune intervention strategies in "self-antigen" in vivo tumor models. We have constructed recombinant vaccinia viruses based on the highly attenuated and modified vaccinia virus ankara (MVA strain), expressing h5T4 (MVA-h5T4), m5T4 (MVA-m5T4), and Escherichia coli LacZ (MVA-LacZ). Immunization of BALB/c and C57BL/6 mice with MVA-h5T4 and MVA-m5T4 constructs induced antibody responses to human and mouse 5T4, respectively. C57BL/6 and BALB/c mice vaccinated with MVA-h5T4 were challenged with syngeneic tumor line transfectants, B16 melanoma, and CT26 colorectal cells that express h5T4. MVA-h5T4-vaccinated mice showed significant tumor retardation compared with mice vaccinated with MVA-LacZ or PBS. In active treatment studies, inoculation with MVA-h5T4 was able to treat established CT26-h5T4 lung tumor and to a lesser extent B16.h5T4 s.c. tumors. Additionally, when C57BL/6 mice vaccinated with MVA-m5T4 were challenged with B16 cells expressing m5T4, resulting growth of the tumors was significantly retarded compared with control animals. Furthermore, mice vaccinated with MVA-m5T4 showed no signs of autoimmune toxicity. These data support the use of MVA-5T4 for tumor immunotherapy. PMID:12481437

  14. [Immunoglobulin genes encoding antibodies directed to oncodevelopmental carbohydrate antigens].

    Science.gov (United States)

    Zenita, K; Yago, K; Fujimoto, E; Kannagi, R

    1990-07-01

    We investigated the immunoglobulin genes which encode the variable region of the monoclonal antibodies directed to the onco-developmental carbohydrate antigens such SSEA-1, fucosyl SSEA-1, SSEA-3 and SSEA-4. The VH region of these antibodies was preferentially encoded by the gene members of the X24, VH7183 and Q52 families, the families which are known to be located at the 3'-end region of the murine germ line VH gene. This result is interesting particularly when considering that the members of the 3'-end VH families are known to be preferentially expressed in embryonic B lymphocytes by an intrinsic genetic program. The comparative study of the nucleic acid sequences of mRNAs encoding these antibodies and the sequences of the corresponding germ line VH genes disclosed that the sequences encoding the antibodies contain no mutation from the germ line VH genes, or contain only a few somatic mutations, which are thought to be insignificant for the reactivity of the antibodies to the nominal antigens. These results imply that some of the embryonic B lymphocytes that express the unmutated germ line VH genes of the 3'-end families can be reactive with embryonic carbohydrate antigens, albeit rearranged with appropriate D-JH gene segments, and coupled with proper light chains. The VH region of the syngenic monoclonal anti-idiotypic antibodies directed to these anti-carbohydrate antibodies were also encoded preferentially by the members of the 3'-end VH families. We propose here that a part of the virgin embryonic B lymphocytes, which express the antibody encoded by the gene members of the 3'-end VH families at the cell surface, will be stimulated by the embryonic carbohydrate antigens which are abundantly present in the internal milieu of the embryo. The clonally expanded B lymphocytes, in turn, will facilitate the proliferation of other populations of embryonic B lymphocytes expressing the corresponding anti-idiotypic antibodies, which are also encoded by the gene members

  15. Expression analysis of carbohydrate antigens in ductal carcinoma in situ of the breast by lectin histochemistry

    Directory of Open Access Journals (Sweden)

    Kieber-Emmons Thomas

    2008-05-01

    Full Text Available Abstract Background The number of breast cancer patients diagnosed with ductal carcinoma in situ (DCIS continues to grow. Laboratory and clinical data indicate that DCIS can progress to invasive disease. Carbohydrate-mediated cell-cell adhesion and tumor-stroma interaction play crucial roles in tumorigenesis and tumor aggressive behavior. Breast carcinogenesis may reflect quantitative as well as qualitative changes in oligosaccharide expression, which may provide a useful tool for early detection of breast cancer. Because tumor-associated carbohydrate antigens (TACA are implicated in tumor invasion and metastasis, the purpose of this study was to assess the expression of selected TACA by lectin histochemistry on DCIS specimens from the archival breast cancer tissue array bank of the University of Arkansas for Medical Sciences. Methods For detection of TACA expression, specimens were stained with Griffonia simplicifolia lectin-I (GS-I and Vicia vilosa agglutinin (VVA. We studied associations of lectin reactivity with established prognostic factors, such as tumor size, tumor nuclear grade, and expression of Her-2/neu, p53 mutant and estrogen and progesterone receptors. Results We observed that both lectins showed significant associations with nuclear grade of DCIS. DCIS specimens with nuclear grades II and III showed significantly more intense reactivity than DCIS cases with nuclear grade I to GS-1 (Mean-score chi-square = 17.60, DF = 2; P = 0.0002 and VVA (Mean-score chi-square = 15.72, DF = 2; P = 0.0004. Conclusion The results suggest that the expression of VVA- and GS-I-reactive carbohydrate antigens may contribute to forming higher grade DCIS and increase the recurrence risk.

  16. Significance of carbohydrate antigen 50 expression in colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To evaluate the significance of carbohydrate antigen 50(CA50)expression in colorectal carcinoma.Methods Immunohistochemical staining was used to detect CA50 expression in 10 cases of normal colorectal mucosa and 40 cases of cancer mucosa.Results The expression of CA50 increased in normal colorectal mucosa,cancer distant mucosa,cancer adjacent mucosa and cancer mucosa,and there were significant differences among them(P<0.05).The expression of CA50 in colorectal carcinoma was correlated with the deg...

  17. Soluble Plasmodium falciparum antigens contain carbohydrate moieties important for immune reactivity

    DEFF Research Database (Denmark)

    Jakobsen, P H; Theander, T G; Jensen, J B;

    1987-01-01

    The importance of carbohydrate moieties for the antigenicity of purified soluble Plasmodium falciparum antigens from the asexual blood stage was tested. Digestion of the soluble antigens with alpha-D-galactosidase clearly affected the ability of the antigen to react with malaria-immune sera from ....... The results might have important implications for the strategy of developing a malaria vaccine.......The importance of carbohydrate moieties for the antigenicity of purified soluble Plasmodium falciparum antigens from the asexual blood stage was tested. Digestion of the soluble antigens with alpha-D-galactosidase clearly affected the ability of the antigen to react with malaria-immune sera from...

  18. Development of a Serum Biomarker Assay That Differentiates Tumor-Associated MUC5AC (NPC-1C ANTIGEN from Normal MUC5AC

    Directory of Open Access Journals (Sweden)

    Janos Luka

    2011-01-01

    Full Text Available A serum ELISA using a monoclonal antibody that detects a MUC5AC-related antigen (NPC-1C antigen expressed by pancreatic and colorectal cancer was developed. The NPC-1C antibody reacts with specific epitopes expressed by tumor-associated MUC5AC that does not appear on MUC5AC from normal tissues. Based on observations of a highly specific antibody, we tested the ELISA to differentiate serum from healthy blood donors compared to serum from patients with colorectal or pancreatic cancer. Additionally, patient tumor tissue was stained to examine the expression pattern of MUC5AC-related antigen in pancreatic and colorectal cancers. The results indicate the NPC-1C antibody ELISA distinguished serum of cancer patients from normal donors with very good sensitivity and specificity. Most patient's tumor biopsy exhibited NPC-1C antibody reactivity, indicating that tumor-associated MUC5AC antigen from tumor is shed into blood, where it can be detected by the NPC-1C antibody ELISA. This serum test provides a new tool to aid in the diagnosis of these cancers and immune monitoring of cancer treatment regimens.

  19. Specificity for the tumor-associated self-antigen WT1 drives the development of fully functional memory T cells in the absence of vaccination.

    Science.gov (United States)

    Pospori, Constandina; Xue, Shao-An; Holler, Angelika; Voisine, Cecile; Perro, Mario; King, Judith; Fallah-Arani, Farnaz; Flutter, Barry; Chakraverty, Ronjon; Stauss, Hans J; Morris, Emma C

    2011-06-23

    Recently, vaccines against the Wilms Tumor antigen 1 (WT1) have been tested in cancer patients. However, it is currently not known whether physiologic levels of WT1 expression in stem and progenitor cells of normal tissue result in the deletion or tolerance induction of WT1-specific T cells. Here, we used an human leukocyte antigen-transgenic murine model to study the fate of human leukocyte antigen class-I restricted, WT1-specific T cells in the thymus and in the periphery. Thymocytes expressing a WT1-specific T-cell receptor derived from high avidity human CD8 T cells were positively selected into the single-positive CD8 population. In the periphery, T cells specific for the WT1 antigen differentiated into CD44-high memory phenotype cells, whereas T cells specific for a non-self-viral antigen retained a CD44(low) naive phenotype. Only the WT1-specific T cells, but not the virus-specific T cells, displayed rapid antigen-specific effector function without prior vaccination. Despite long-term persistence of WT1-specific memory T cells, the animals did not develop autoimmunity, and the function of hematopoietic stem and progenitor cells was unimpaired. This is the first demonstration that specificity for a tumor-associated self-antigen may drive differentiation of functionally competent memory T cells. PMID:21447831

  20. Therapeutic Strategies for Human IgM Antibodies Directed at Tumor-Associated Ganglioside Antigens: Discoveries Made During the Morton Era and Future Directions.

    Science.gov (United States)

    Jones, Peter C; Irie, Reiko F

    2016-01-01

    Tumor-associated gangliosides have been investigated for their potential as antigenic targets for more than 35 years, culminating in the recent Food and Drug Administration approval of dinutuximab (Unituxin), an IgG antibody targeted against GD2, for the treatment of neuroblastoma in children. This review is focused on discoveries and development of therapeutic approaches involving human IgM antibodies directed against gangliosides, which occurred over the past 40 years at University of California-Los Angeles and the John Wayne Cancer Institute, where Dr. Donald Morton led the surgical oncology department until his death. PMID:27481004

  1. Identification of a panel of tumor-associated antigens from breast carcinoma cell lines, solid tumors and testis cDNA libraries displayed on lambda phage

    Directory of Open Access Journals (Sweden)

    Cianfriglia Maurizio

    2004-11-01

    Full Text Available Abstract Background Tumor-associated antigens recognized by humoral effectors of the immune system are a very attractive target for human cancer diagnostics and therapy. Recent advances in molecular techniques have led to molecular definition of immunogenic tumor proteins based on their reactivity with autologous patient sera (SEREX. Methods Several high complexity phage-displayed cDNA libraries from breast carcinomas, human testis and breast carcinoma cell lines MCF-7, MDA-MB-468 were constructed. The cDNAs were expressed in the libraries as fusion to bacteriophage lambda protein D. Lambda-displayed libraries were efficiently screened with sera from patients with breast cancer. Results A panel of 21 clones representing 18 different antigens, including eight proteins of unknown function, was identified. Three of these antigens (T7-1, T11-3 and T11-9 were found to be overexpressed in tumors as compared to normal breast. A serological analysis of the 21 different antigens revealed a strong cancer-related profile for at least five clones (T6-2, T6-7, T7-1, T9-21 and T9-27. Conclusions Preliminary results indicate that patient serum reactivity against five of the antigens is associated with tumor disease. The novel T7-1 antigen, which is overexpressed in breast tumors and recognized specifically by breast cancer patient sera, is potentially useful in cancer diagnosis.

  2. The immunoradiometric assay for carbohydrate antigen CA-242

    International Nuclear Information System (INIS)

    Using 125I-labelled monoclonal antibody (C242) against carbohydrate antigen CA-242, the sandwich immunoradiometric assay (IRMA) was developed. In preliminary clinical application of this method, the results of serum CA-242 measurements were 2.5 ± 4.5 U/ml for 77 normal individuals, 3.5 ± 7.0 U/ml for 128 cases of benign diseases, and 56.0 ± 91.3 U/ml for 210 cases of malignant tumors. The CA-242 values of patients with malignant tumors were significantly higher than that of patients with benign diseases. Taking 12 U/ml as normal upper limit, the positive detective rates of pancreatic and colorectal cancers were 86.6% and 62.0% respectively, while the false positive rate for normal individuals was 4%

  3. Production of Single-Chain Variable-Fragments against Carbohydrate Antigens

    OpenAIRE

    Yoko Fujita-Yamaguchi

    2014-01-01

    The production of human single-chain variable-fragments (scFvs) against carbohydrate antigens by phage display technology is seemingly a logical strategy towards the development of antibody therapeutics, since carbohydrates are self-antigens. Panning and screening of phages displaying human scFvs using a variety of neoglycolipids presenting structurally-defined carbohydrates resulted in a number of candidate phage clones as judged by cautious evaluation of DNA sequences and specific binding t...

  4. Immunohistochemical analysis of carbohydrate antigens in chronic inflammatory gastrointestinal diseases.

    Science.gov (United States)

    Kobayashi, Motohiro; Nakayama, Jun

    2010-01-01

    Over the last four decades, immunohistochemistry (IHC) has become an invaluable technique to detect antigens in tissue sections. Compared to Western blotting analysis, IHC is advantageous in determining histological distribution and localization of the antigen. Another advantage, if one can access human formalin-fixed paraffin-embedded (FFPE) blocks of disease tissues, is that IHC makes it possible to analyze diseases retrospectively from archived pathological tissue specimens. In this chapter, we describe protocols used for both conventional and multiple immunostainings using FFPE tissue sections, which have been used for quantitative analysis of high endothelial venule (HEV)-like vessels and lymphocyte subsets attached to HEV-like vessels in our studies of chronic inflammatory gastrointestinal diseases. We also describe in detail a protocol using an L-selectinIgM chimera in situ binding assay on FFPE tissue sections for functional detection of L-selectin ligand carbohydrates expressed on HEV-like vessels. After presenting each protocol, we provide practical examples for its use obtained from our studies.

  5. An adenoviral cancer vaccine co-encoding a tumor associated antigen together with secreted 4-1BBL leads to delayed tumor progression

    DEFF Research Database (Denmark)

    Ragonnaud, Emeline; Andersson, Anne-Marie C; Pedersen, Anders Elm;

    2016-01-01

    Previous studies have shown promising results when using an agonistic anti-4-1BB antibody treatment against established tumors. While this is promising, this type of treatment can induce severe side effects. Therefore, we decided to incorporate the membrane form of 4-1BB ligand (4-1BBL......) in a replicative deficient adenovirus vaccine expressing the invariant chain (Ii) adjuvant fused to a tumor associated antigen (TAA). The Ii adjuvant increases and prolongs TAA specific CD8+ T cells as previously shown and local expression of 4-1BBL was chosen to avoid the toxicity associated with systemic...... presenting cells, but it did not enhance T cell responses in mice towards the Ii linked antigen. In tumor-bearing mice, our vaccine was found to decrease the frequency of TAA specific CD8+ T cells, but this difference did not alter the therapeutic efficacy. In order to reconcile our findings...

  6. A kinetic analysis of the tumor-associated galactopyranosyl-(1→3)-2-acetamido-2-deoxy--D-galactopyranoside antigen-lectin interaction

    Indian Academy of Sciences (India)

    Bandaru Narasimha Murthy; Narayanaswamy Jayaraman

    2008-01-01

    A kinetic study of the tumor-associated galactopyranosyl-(1→3)-2-acetamido-2-deoxy--Dgalactopyranoside (T-antigen) with lectin peanut agglutinin is described. The disaccharide antigen was synthesized by chemical methods and was functionalized suitably for immobilization onto a carboxymethylated sensor chip. The ligand immobilized surface was allowed interaction with the lectin peanut agglutinin, which acted as the analyte and the interaction was studied by the surface plasmon resonance method. The ligand-lectin interaction was characterized by the kinetic on-off rates and a bivalent analyte binding model was found to describe the observed kinetic constants. It was identified that the antigen-lectin interaction had a faster association rate constant (a1) and a slower dissociation rate constant (d1) in the initial binding step. The subsequent binding step showed much reduced kinetic rates. The antigen-lectin interaction was compared with the kinetic rates of the interaction of a galactopyranosyl-(1→ 4)--D-galactopyranoside derivative and a mannopyranoside derivative with the lectin.

  7. Lung adenocarcinoma with clear cell features producing carbohydrate antigen 19-9.

    Science.gov (United States)

    Goto, Taichiro; Hada, Masao; Oyama, Toshio

    2015-10-01

    A 76-year-old man underwent surgery for lung cancer. Histopathologically, most of the resected tumor was composed of polygonal cells with foamy cytoplasm, and the cells were arranged predominantly in acinar patterns. In this case, although the carbohydrate antigen 19-9 level was high before surgery, it normalized after resection. The tumor was considered a carbohydrate antigen 19-9-producing tumor, which was further supported by the results of immunohistochemical analysis. Adenocarcinoma with clear cell features, producing carbohydrate antigen 19-9, is an exceedingly rare entity.

  8. Characterization of the carbohydrate components of Taenia solium oncosphere proteins and their role in the antigenicity.

    Science.gov (United States)

    Arana, Yanina; Verastegui, Manuela; Tuero, Iskra; Grandjean, Louis; Garcia, Hector H; Gilman, Robert H

    2013-10-01

    This study examines the carbohydrate composition of Taenia solium whole oncosphere antigens (WOAs), in order to improve the understanding of the antigenicity of the T. solium. Better knowledge of oncosphere antigens is crucial to accurately diagnose previous exposure to T. solium eggs and thus predict the development of neurocysticercosis. A set of seven lectins conjugates with wide carbohydrate specificity were used on parasite fixations and somatic extracts. Lectin fluorescence revealed that D-mannose, D-glucose, D-galactose and N-acetyl-D-galactosamine residues were the most abundant constituents of carbohydrate chains on the surface of T. solium oncosphere. Lectin blotting showed that posttranslational modification with N-glycosylation was abundant while little evidence of O-linked carbohydrates was observed. Chemical oxidation and enzymatic deglycosylation in situ were performed to investigate the immunoreactivity of the carbohydrate moieties. Linearizing or removing the carbohydrate moieties from the protein backbones did not diminish the immunoreactivity of these antigens, suggesting that a substantial part of the host immune response against T. solium oncosphere is directed against the peptide epitopes on the parasite antigens. Finally, using carbohydrate probes, we demonstrated for the first time that the presence of several lectins on the surface of the oncosphere was specific to carbohydrates found in intestinal mucus, suggesting a possible role in initial attachment of the parasite to host cells.

  9. Tumor-associated antigens identified by mRNA expression profiling induce protective anti-tumor immunity

    DEFF Research Database (Denmark)

    Mathiassen, S; Lauemøller, S L; Ruhwald, M;

    2001-01-01

    to identify TAA, mice were immunized with mixtures of peptides representing putative cytotoxic T cell epitopes derived from one of the gene products. Indeed, such immunized mice were partially protected against subsequent tumor challenge. Despite being immunized with bona fide self antigens, no...

  10. Identification of new tumor associated antigens and their usage for new therapeutic strategies based on the combination of chemotherapy and immunotherapy for colorectal cancer patients

    International Nuclear Information System (INIS)

    The main general objective of this project was to characterize a new colorectal carcinoma (CRC) tumor-associated antigen (TAA) and validate a new therapeutic strategy combining chemotherapy and tumor vaccination for the treatment of cancer patients. To this purpose a strategic interaction between Drs. Proietti/Maccali at the ISS and the group of Drs. Rosenberg/Robbins at the NIH was established. A stage of Dr. Maccalli at the NIH allowed to carry out the first steps for the identification and the initial characterization of the CRC TAA named COA-1. A laboratory meeting with Dr. Robbins has been planned on May 24-25 2006 at the ISS, during the International Meeting on Immunotherapy of Cancer: Challenges and Needs, for discussing results and perspectives of this research project

  11. Prognostic value of increased carbohydrate antigen in patients with heart failure

    OpenAIRE

    Méndez, Ana B; Ordoñez-Llanos, Jordi; Ferrero, Andreu; Noguero, Mariana; Mir, Teresa; Mora, Josefina; Bayes-Genis, Antoni; Mirabet, Sònia; Cinca, Juan; Roig, Eulàlia

    2014-01-01

    AIM: To study the prognostic value of carbohydrate antigen 125 (CA125) and whether it adds prognostic information to N-terminal pro-brain natriuretic peptide (NT-proBNP) in stable heart failure (HF) patients.

  12. The Immunogenicity of the Tumor-Associated Antigen α-Fetoprotein Is Enhanced by a Fusion with a Transmembrane Domain

    Directory of Open Access Journals (Sweden)

    Lucile Tran

    2012-01-01

    Full Text Available Aim. To investigate the ability of recombinant modified vaccinia virus Ankara (rMVA vector to induce an immune response against a well-tolerated self-antigen. Methods. rMVA vectors expressing different form of α-fetoprotein (AFP were produced and characterized. Naïve mice were vaccinated with MVA vectors expressing the AFP antigen in either a secreted, or a membrane-bound, or an intracellular form. The immune response was monitored by an IFNΓ ELISpot assay and antibody detection. Results. Vaccination with the membrane-associated form of AFP induced a stronger CD8+ T-cell response compared to the ones obtained with the MVA encoding the secreted or the intracellular forms of AFP. Moreover, the vaccination with the membrane-bound AFP elicited the production of AFP-specific antibodies. Conclusions. The AFP transmembrane form is more immunogenic. Expressing a membrane-bound form in the context of an MVA vaccination could enhance the immunogenicity of a self-antigen.

  13. Carbohydrate Biopolymers Enhance Antibody Responses to Mucosally Delivered Vaccine Antigens

    Science.gov (United States)

    Bacon, A.; Makin, J.; Sizer, P. J.; Jabbal-Gill, I.; Hinchcliffe, M.; Illum, L.; Chatfield, S.; Roberts, M.

    2000-01-01

    We have evaluated the ability of two carbohydrate biopolymers, chitosan and gellan, to enhance antibody responses to subunit influenza virus vaccines delivered to the respiratory tracts of mice. Groups of mice were vaccinated three times intranasally (i.n.) with 10 μg of purified influenza B/Panama virus surface antigens (PSAs), which consist of hemagglutinin (HA) and neuraminidase (NA), either alone or admixed with chitosan or gellan solutions. Separate groups were vaccinated subcutaneously (s.c.) with PSAs adsorbed to Alhydrogel or chitosan or gellan alone i.n. Serum antibody responses were determined by enzyme-linked immunosorbent assay (ELISA) for influenza virus-specific immunoglobulin G (IgG) and by HA inhibition (HAI) and NA inhibition (NAI) assays. The local respiratory immune response was measured by assaying for influenza virus-specific IgA antibody in nasal secretions and by enumerating nasal and pulmonary lymphocytes secreting IgA, IgG, and IgM anti-influenza virus-specific antibodies by enzyme-linked immunospotting (ELISPOT). When administered alone i.n., B/Panama PSA was poorly immunogenic. Parenteral immunization with B/Panama PSA with Alhydrogel elicited high titers of anti-B/Panama antibodies in serum but a very poor respiratory anti-B/Panama IgA response. In contrast, i.n. immunization with PSA plus chitosan stimulated very strong local and systemic anti-B/Panama responses. Gellan also enhanced the local and serum antibody responses to i.n. PSA but not to the same extent as chitosan. The ability of chitosan to augment the immunogenicity of influenza vaccines given i.n. was confirmed using PSA prepared from an influenza A virus (A/Texas H1N1). PMID:10992483

  14. Simple mucin-type carbohydrate antigens in major salivary glands

    DEFF Research Database (Denmark)

    Therkildsen, M H; Mandel, U; Thorn, J;

    1994-01-01

    , on the other hand, expressed A, H, and inconstantly sialosyl-T, Tn, and sialosyl-Tn antigens in major salivary glands, whereas serous cells of minor (labial) salivary glands expressed H exclusively, Tn and sialosyl-T antigens inconstantly, but never sialosyl-Tn and A antigens. The difference may be related...... to a more simple cytodifferentiation of serous cells of minor (labial) salivary glands as compared with major salivary glands. Duct cells in major salivary glands expressed A, H, and inconstantly T, sialosyl-T, and Tn antigens, whereas minor (labial) salivary glands ducts exclusively expressed H, T...... and sialosyl-T antigens, differences that may be related to dissimilarities in the duct system. Myoepithelial cells and basal cells exclusively expressed T and sialosyl-T antigens, which may prove useful in studies of salivary gland tumors, since these cells are known to play a key role in the histological...

  15. Chimeric peptide containing both B and T cells epitope of tumor-associated antigen L6 enhances anti-tumor effects in HLA-A2 transgenic mice.

    Science.gov (United States)

    Lin, Su-I; Huang, Ming-Hsi; Chang, Yu-Wen; Chen, I-Hua; Roffler, Steve; Chen, Bing-Mae; Sher, Yuh-Pyng; Liu, Shih-Jen

    2016-07-28

    Synthetic peptides are attractive for cancer immunotherapy because of their safety and flexibility. In this report, we identified a new B cell epitope of tumor-associated antigen L6 (TAL6) that could induce antibody-dependent cellular cytotoxicity (ADCC) in vivo. We incorporated the B cell epitope with a cytotoxic T lymphocyte (CTL) and a helper T (Th) epitope to form a chimeric long peptide. We formulated the chimeric peptide with different adjuvants to immunize HLA-A2 transgenic mice and evaluate their immunogenicity. The chimeric peptide formulated with an emulsion type nanoparticle (PELC) adjuvant and a toll-like receptor 9 agonist (CpG ODN) (PELC/CpG) induced the greatest ADCC and CTL responses. The induced anti-tumor immunity inhibited the growth of TAL6-positive cancer cells. Moreover, we observed that immunization with the chimeric peptide inhibited cancer cell migration in vitro and metastasis in vivo. These data suggest that a chimeric peptide containing both B and T cell epitopes of TAL6 formulated with PELC/CpG adjuvant is feasible for cancer immunotherapy. PMID:27130449

  16. Simple mucin-type carbohydrate antigens in pleomorphic adenomas

    DEFF Research Database (Denmark)

    Therkildsen, M H; Mandel, U; Christensen, M;

    1993-01-01

    Simple mucin-type carbohydrate structures, T, Tn and sialosyl-Tn, are regarded as general markers of carcinomas in several epithelial tissues as a result of incomplete synthesis with precursor accumulation. The structures have a very limited distribution in normal tissues and secretions, includin...

  17. Establishment of HLA-DR4 transgenic mice for the identification of CD4+ T cell epitopes of tumor-associated antigens.

    Directory of Open Access Journals (Sweden)

    Junji Yatsuda

    Full Text Available Reports have shown that activation of tumor-specific CD4(+ helper T (Th cells is crucial for effective anti-tumor immunity and identification of Th-cell epitopes is critical for peptide vaccine-based cancer immunotherapy. Although computer algorithms are available to predict peptides with high binding affinity to a specific HLA class II molecule, the ability of those peptides to induce Th-cell responses must be evaluated. We have established HLA-DR4 (HLA-DRA*01:01/HLA-DRB1*04:05 transgenic mice (Tgm, since this HLA-DR allele is most frequent (13.6% in Japanese population, to evaluate HLA-DR4-restricted Th-cell responses to tumor-associated antigen (TAA-derived peptides predicted to bind to HLA-DR4. To avoid weak binding between mouse CD4 and HLA-DR4, Tgm were designed to express chimeric HLA-DR4/I-E(d, where I-E(d α1 and β1 domains were replaced with those from HLA-DR4. Th cells isolated from Tgm immunized with adjuvant and HLA-DR4-binding cytomegalovirus-derived peptide proliferated when stimulated with peptide-pulsed HLA-DR4-transduced mouse L cells, indicating chimeric HLA-DR4/I-E(d has equivalent antigen presenting capacity to HLA-DR4. Immunization with CDCA155-78 peptide, a computer algorithm-predicted HLA-DR4-binding peptide derived from TAA CDCA1, successfully induced Th-cell responses in Tgm, while immunization of HLA-DR4-binding Wilms' tumor 1 antigen-derived peptide with identical amino acid sequence to mouse ortholog failed. This was overcome by using peptide-pulsed syngeneic bone marrow-derived dendritic cells (BM-DC followed by immunization with peptide/CFA booster. BM-DC-based immunization of KIF20A494-517 peptide from another TAA KIF20A, with an almost identical HLA-binding core amino acid sequence to mouse ortholog, successfully induced Th-cell responses in Tgm. Notably, both CDCA155-78 and KIF20A494-517 peptides induced human Th-cell responses in PBMCs from HLA-DR4-positive donors. Finally, an HLA-DR4 binding DEPDC1191

  18. Simple mucin-type carbohydrates in normal and malignant human endometrium

    DEFF Research Database (Denmark)

    Ravn, V; Mandel, U; Svenstrup, B;

    1995-01-01

    The simple mucin-type carbohydrate antigens, Tn, sialosyl-Tn, and T, are tumor-associated antigens of adenocarcinomas. We evaluated by immunohistochemistry the expression of Tn, sialosyl-Tn (s-Tn), T, and sialosyl-T (s-T) antigens in normal nonsecretory, early gestational, and malignant human end...

  19. A prospective study of serum tumour markers carcinoembryonic antigen, carbohydrate antigens 50 and 242, tissue polypeptide antigen and tissue polypeptide specific antigen in the diagnosis of pancreatic cancer with special reference to multivariate diagnostic score.

    OpenAIRE

    Pasanen, P. A.; Eskelinen, M.; Partanen, K.; Pikkarainen, P; Penttilä, I.; Alhava, E

    1994-01-01

    The aim of this study was to assess by a stepwise multivariate discriminant analysis the value of four current serum tumour markers - carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 50 and CA 242 and tissue polypeptide antigen (TPA) - and a new serum tumour marker, tissue polypeptide specific antigen (TPS), in the diagnosis of pancreatic cancer. The serum values were measured in a prospective series of patients with jaundice, with unjaundiced cholestasis and with a suspicion of chro...

  20. Differential Recognition and Hydrolysis of Host Carbohydrate Antigens by Streptococcus pneumoniae Family 98 Glycoside Hydrolases

    Energy Technology Data Exchange (ETDEWEB)

    Higgins, M.; Whitworth, G; El Warry, N; Randriantsoa, M; Samain, E; Burke, R; Vocadlo, D; Boraston, A

    2009-01-01

    The presence of a fucose utilization operon in the Streptococcus pneumoniae genome and its established importance in virulence indicates a reliance of this bacterium on the harvesting of host fucose-containing glycans. The identities of these glycans, however, and how they are harvested is presently unknown. The biochemical and high resolution x-ray crystallographic analysis of two family 98 glycoside hydrolases (GH98s) from distinctive forms of the fucose utilization operon that originate from different S. pneumoniae strains reveal that one enzyme, the predominant type among pneumococcal isolates, has a unique endo-{beta}-galactosidase activity on the LewisY antigen. Altered active site topography in the other species of GH98 enzyme tune its endo-{beta}-galactosidase activity to the blood group A and B antigens. Despite their different specificities, these enzymes, and by extension all family 98 glycoside hydrolases, use an inverting catalytic mechanism. Many bacterial and viral pathogens exploit host carbohydrate antigens for adherence as a precursor to colonization or infection. However, this is the first evidence of bacterial endoglycosidase enzymes that are known to play a role in virulence and are specific for distinct host carbohydrate antigens. The strain-specific distribution of two distinct types of GH98 enzymes further suggests that S. pneumoniae strains may specialize to exploit host-specific antigens that vary from host to host, a factor that may feature in whether a strain is capable of colonizing a host or establishing an invasive infection.

  1. Carbohydrate Antigen Sialyl Lewis a – Its Pathophysiological ignificance and Induction Mechanism in Cancer Progression

    OpenAIRE

    Reiji Kannagi

    2007-01-01

    Carbohydrate antigen sialyl Lewis a (CA19-9) is the mostfrequently applied serum tumor marker for diagnosis of cancersin the digestive organs. Recent progress disclosed thepresence of a normal counterpart of the determinant, namelydisialyl Lewis a, which is predominantly expressed in nonmalignantepithelial cells of the digestive organs, while sialylLewis a is preferentially expressed in cancers. The disialylLewis a determinant carries one extra sialic residue attachedthrough a 2 6 linkage to ...

  2. Carbohydrates

    Science.gov (United States)

    Carbohydrates are one of the main types of nutrients. They are the most important source of energy for your body. Your digestive system changes carbohydrates into glucose (blood sugar). Your body uses this ...

  3. Benign Hydronephrosis and Elevated of Serum Levels of Carbohydrate Antigen CA 19-9: A Case Report

    Science.gov (United States)

    Filipovic, Branka; Milinić, Nikola; Gacic, Jasna; Markovic, Olivera; Djokovic, Aleksandra; Filipovic, Branislav

    2016-01-01

    Patient: Male, 58 Final Diagnosis: Hydronephrosis Symptoms: Blunt abdominal pain • constipation • constipation Medication: — Clinical Procedure: Extracorporeal shock wave lithotripsy and percutaneous nephrostolithotomy Specialty: Gastroenterology and Hepatology Objective: Rare co-existance of disease or pathology Background: Carbohydrate tumor-associated antigen (CA 19-9) has been shown to be upregulated in other malignant tumors including gastric, ovarian, hepatocellular, and colorectal carcinoma as well as benign diseases of the biliary track such as pancreatitis, cholangitis, and choledocholithiasis. According to the available literature, in several cases of benign hydronephrosis and in a few cases of benign renal diseases, elevated CA 19-9 has been noted. Case Report: A 58-year-old Caucasian male patient was admitted in our clinic with complaints about blunt abdominal pain in the past two-month period localized in the right lumbar region and irradiating into the right inguinal area, constipation, abdominal bloating, and intermittent hematuria. The concentration of serum CA 19-9 was 3500 U/mL. Urine cytology provided no signs of abnormality. Intravenous urography visualized right-sided pyelon and ureter duplex with the defect in contrast shade of the pyelon, caused by a stag horn calculus. Contrast added computerized axial tomography of the abdomen and pelvis visualized the pyelon casted concretion spreading throughout the right pyelon, with ureterohydronephrosis with the distal block for passage of the contrast to the distal part of the ureter. Conclusions: There is no doubt that CA 19-9 level is occasionally elevated in patients with obstructive urolithiasis as it was in our case. In the routine medical praxis, urolithiasis should not be neglected in the differential diagnosis of elevated concentrations of CA 19-9 marker. PMID:27287959

  4. Carbohydrates

    Science.gov (United States)

    ... is fine because they contain important vitamins and minerals. But your body rapidly digests the starch in white potatoes. This can raise your blood glucose level. Healthy carbohydrates include: Natural sugars in fruits, vegetables, milk, and milk products Dietary fiber Starches in whole- ...

  5. Increased serum carbohydrate antigen 19-9 in relapsed ductal breast carcinoma.

    Science.gov (United States)

    Papantoniou, Vassilios; Tsiouris, Spyridon; Koutsikos, John; Ptohis, Nikolaos; Lazaris, Dimitrios; Zerva, Cherry

    2006-01-01

    Increased serum carbohydrate antigen (CA) 19-9 is a quite uncommon manifestation of breast cancer both on early disease and on relapse. A 53-year-old woman with invasive ductal breast carcinoma underwent left-sided mastectomy. Two years later she palpated a subcutaneous mass at the mastectomy scar, arousing suspicion of local relapse. Surgery and histopathology revealed infiltration by breast adenocarcinoma and she was treated with chemotherapy. At that time serum tumor markers, carcinoembryonic antigen (CEA) and CA 15-3 were within normal range. Over the next six months she displayed an increase of serum CEA while serum CA 15-3 remained within normal range. In an attempt to search for a second neoplasm possibly of gastrointestinal (GI) origin, abdominal computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangio-pancreatography (MRCP), endoscopy of the upper GI tract and colonoscopy were performed, as well as measurement of serum CA 19-9. While no indication of a GI neoplasm was detected, she displayed an over 10-fold increase of serum CA 19-9. The patient had also an X-ray mammography and technetium-99m hexakis-2-methoxyisobutylisonitrile ((99m)Tc-MIBI) scintimammography (SM). Whilst mammography was negative for contralateral disease recurrence, SM was suggestive of axillary lymph node involvement. Axillary lymph node dissection confirmed an extensive metastatic infiltration of these nodes by breast adenocarcinoma. Three months later serum CA 19-9 and CEA became normal. The interest of this case lies on the unexpected high serum CA 19-9 values found in a breast relapsed adenocarcinoma and in the important contribution of SM in diagnosing the axillary lymph node metastatic infiltration. PMID:16617392

  6. Active treatment of murine tumors with a highly attenuated vaccinia virus expressing the tumor associated antigen 5T4 (TroVax) is CD4+ T cell dependent and antibody mediated.

    Science.gov (United States)

    Harrop, Richard; Ryan, Matthew G; Myers, Kevin A; Redchenko, Irina; Kingsman, Susan M; Carroll, Miles W

    2006-09-01

    5T4 is a tumor associated antigen that is expressed on the surface of a wide spectrum of human adenocarcinomas. The highly attenuated virus, modified vaccinia Ankara, has been engineered to express human 5T4 (h5T4). In a pre-clinical murine model, the recombinant virus (TroVax) induces protection against challenge with CT26-h5T4 (a syngeneic tumor line expressing h5T4). Anti-tumor activity is long lived, with protection still evident 6 months after the final vaccination. In a therapeutic setting, injection of mice with TroVax results in a reduction in tumor burden of >90%. Depletion of CD8+ T cells has no effect upon therapy in the active treatment model, whereas depletion of CD4+ T cells completely abrogates anti-tumor activity. In a prophylactic setting, depletion of CD4+ and CD8+ T cells after the induction of a h5T4 immune response has no deleterious effect on protection following challenge with CT26-h5T4. In light of these studies, the role of antibodies in protection against tumor challenge was investigated. 5T4 specific polyclonal serum decreased tumor burden by approximately 70%. Thus, we conclude that CD4+ T cells are essential for the induction of a protective immune response and that antibodies are the likely effector moiety in this xenogeneic murine tumor model. PMID:16311730

  7. Acute Cholecystitis with Significantly Elevated Levels of Serum Carbohydrate Antigen 19-9

    Directory of Open Access Journals (Sweden)

    Shuji Akimoto

    2016-08-01

    Full Text Available Serum carbohydrate antigen 19-9 (CA 19-9, a marker of malignant tumors, is generally slightly elevated in benign conditions. We report a case of acute cholecystitis with a significantly elevated level of serum CA 19-9 based on positron emission tomography (PET-computed tomography (CT findings. A 65-year-old woman presented with abdominal pain and fever. A CT image revealed an enlarged gallbladder without tumor shadows. The C-reactive protein (CRP level was elevated to 7.66 mg/dl. Moreover, the serum CA 19-9 level was significantly elevated to 19,392 U/ml. We started antibiotic treatment, because we suspected acute cholecystitis, but still, we could not ignore the possible presence of malignant tumors. After 11 days of antibiotic treatment, serum CRP and CA 19-9 levels decreased to 0.11 mg/dl and 1,049 U/ml, respectively. There was an accumulation of fluorine 18-labeled fluorodeoxyglucose (maximum standardized uptake value, 9.3 without tumor shadows in the liver, near the gallbladder, on the PET-CT examination. We considered the possibility that the inflammation had spread from the gallbladder to the liver, made a diagnosis of acute cholecystitis, and performed a cholecystectomy 33 days after treatment initiation. The serum CA 19-9 level decreased to 45 U/ml after the surgery. One year after the surgery, the patient was alive, and the serum CA 19-9 level was 34 U/ml. Acute cholecystitis with a significantly high elevation of the serum CA 19-9 level is rare. In such cases, it is important to confirm the change in the serum CA 19-9 level over time after antibiotic treatment and perform imaging studies to distinguish between inflammation and malignancy.

  8. The Thomsen-Friedenreich (T) simple mucin-type carbohydrate antigen in salivary gland carcinomas

    DEFF Research Database (Denmark)

    Therkildsen, M H; Mandel, U; Christensen, M;

    1995-01-01

    The simple mucin-type T (Thomsen-Friedenreich) antigen is a marker of carcinomas, and has been related to aggressiveness of malignant tumours. We studied the expression of T, sialosyl-T, A and H blood group antigens in salivary gland carcinomas. The aim was to study whether the tumours, based on ...

  9. Invasive breast cancer in Argentine women: association between risk and prognostic factors with antigens of a peptidic and carbohydrate nature

    Directory of Open Access Journals (Sweden)

    Croce MV

    2011-12-01

    Full Text Available Sandra O Demichelis, Marina T Isla-Larrain, Luciano Cermignani, Cecilio G Alberdi, Amada Segal-Eiras, María Virginia CroceCentre of Basic and Applied Immunological Research, Faculty of Medical Sciences, National University of La Plata, La Plata, ArgentinaObjective: In breast cancer, several tumor markers have been identified. The marker most extensively associated with breast cancer is MUC1. The objective of the study was to analyze prognostic and risk factors in relation to tumor markers in order to clarify breast cancer biology. A total of 349 primary tumor samples and lymph nodes from breast cancer patients were studied. Risk and prognostic factors were considered. An immunohistochemical approach was applied and an extensive statistical analysis was performed, including frequency analysis and analysis of variance. Correlation among variables was performed with principal component analysis.Results: All the antigens showed an increased expression according to tumor size increment; moreover, sialyl Lewis x expression showed a significant increase in relation to disease stage, whereas Tn and TF presented a positive tendency. Vascular invasion was related to sialyl Lewis x expression and number of metastatic lymph nodes. Taking into account risk factors, when a patient had at least one child, Lewis antigens diminished their expression. In relation to breastfeeding, sialyl Lewis x expression diminished, although its apical expression increased.Conclusion: Associations between MUC1 and carbohydrate antigens and risk and prognostic factors show the complexity of the cellular biological behavior that these antigens modulate in breast cancer.Keywords: breast cancer, Argentine women, risk factors, prognostic factors, antigenic expression

  10. 多种肿瘤相关抗原抗体在乳癌早期诊断中的应用%Application of antibodies against a panel of multiple tumor-associated antigens in early diagnosis of breast cancer

    Institute of Scientific and Technical Information of China (English)

    徐莉娟; 代丽萍; 王凯娟; 张建营; 王鹏

    2012-01-01

    目的:评价多种肿瘤相关抗原 (TAA) 抗体的联合检测在乳癌早期诊断中的价值,探索一种真实可靠的乳癌早期诊断方法.方法:应用酶联免疫吸附试验对115例乳癌患者和153例正常对照血清中的14种TAA抗体进行检测,应用流行病学方法对检测结果进行综合评价.结果:单独应用14种TAA中的任何一种进行检测时,灵敏度普遍偏低(最高低于33%);对14种TAA进行不同的组合,逐渐增加抗原数目进行检测,随着检测抗体的增多,诊断的灵敏度随之增加,抗原数目增加到8种(Cyclin E,Koc,Imp1,cIAP,p62,p16,Cyclin B1和Calnuc)时,灵敏度达到最高;联合8种TAA检测的灵敏度提高到72.2%,特异度达到91.2%,阳性、阴性似然比分别为8.490、0.304,阳性、阴性预测值分别为86.5%、81.4%,Kappa值0.650.结论:该诊断实验结果与真实值中度一致,8种TAA联合检测乳癌的诊断价值较高.%Aim:To evaluate the diagnostic value of antibodies against multiple tumor-associated antigens ( TAAs ) in the early diagnosis of breast cancer and to develop a valid and reliable diagnostic method for breast cancer. Methods: Enzyme-linked immunosorbent assay ( ELISA ) was used to detect antibodies against fourteen TAAs in 115 sera samples from patients with breast cancer,and also in 153 sera samples from normal individuals. Epidemiological methods were used to e-valuate the testing results for each anti-TAA antibody. Results:The sensitivities were low( the highest below 33% )when a separate TAA was used;with the successive addition of TAAs, there was a stepwise increase of sensitivity. The sensitivity did not increase until when there were eight TAAs ( Cyclin E,Koc,Impl ,cIAP,p62,pl6,Cyclin Bl and Calnuc ). The positive antibody reaction of the eight TAAs reached a sensitivity of 72. 2% and a specificity of 91. 2% . Positive likelihood ratio and negative likelihood ratio were 8. 490 and 0. 304. Positive and negative predictive values were 86. 5% and

  11. Diagnostic sensitivity of serum carcinoembryonic antigen, carbohydrate antigen 19-9, alpha-fetoprotein, and beta-human chorionic gonadotropin in esophageal carcinoma (receiver operating characteristic curve analysis

    Directory of Open Access Journals (Sweden)

    Bhawna Bagaria

    2015-01-01

    Full Text Available Background: Esophageal carcinomas are very lethal disease relatively unresponsive to therapy. The continued development of new and more effective chemotherapeutic agents and regimens offers hope that in the future, this carcinoma may be amenable to either more effective palliative treatment or possibly increased cure. We, therefore, aimed to evaluate the marker with best diagnostic sensitivity in esophageal carcinoma. Materials and Methods: Serum carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, alpha-fetoprotein (AFP, and beta-human chorionic gonadotropin (β-HCG levels were assessed in healthy subjects (n = 50 and patients (n = 50 initially diagnosed of esophageal carcinoma by endoscopic examination and biopsy before receiving any therapy. The data were analyzed using SPSS software version 10.0 (SPSS Inc. USA and MedCalc to estimate mean ± standard deviation, the significance of the observed differences (P value, for calculating sensitivity and for plotting receiver operating characteristic curves. Results: Sensitivity of CEA, CA19-9, AFP, and β-HCG detected in esophagus cancer was 38%, 18%, 10%, and 26% respectively. Conclusion: From the above studied markers, CEA has the highest sensitivity followed by β-HCG, CA19-9 and AFP. Although the sensitivity of tumor markers in esophagus cancer is low, they may be useful additional parameter in the prediction of neoplasms involved at the early stage of tumor growth.

  12. Persistent High Level of Urinary Tumor Marker Carbohydrate Antigen 19-9 in Prenatally Diagnosed Dysplastic Kidney

    Directory of Open Access Journals (Sweden)

    Reza Khorramirouz

    2014-01-01

    Full Text Available Tumor marker carbohydrate antigen 19-9 (CA 19-9 level has gained clinical significance in gastrointestinal malignancies and in various solid and cystic diseases. Dysplastic kidney is a congenital abnormality resulting from atresia of the ureteral bud during the embryogenesis which can be unilateral or bilateral. We report unilateral dysplastic kidney with extremely large cyst diagnosed by routine ultrasonography in the 32nd week of gestational age with high levels of CA 19-9 in cystic and amniotic fluid, as well as persistent high urinary levels of this tumor marker during the 1-year follow-up. Persistent high urinary CA 19-9 level even after cyst aspiration may be attributable to remained function of dysplastic kidney due to remained epithelial lining.

  13. Premalignant and malignant oral lesions are associated with changes in the glycosylation pattern of carbohydrates related to ABH blood group antigens

    DEFF Research Database (Denmark)

    Dabelsteen, Erik; Clausen, H; Holmstrup, P;

    1988-01-01

    The distribution of carbohydrate structures related to the ABO(H) blood group antigen system was studied in biopsies from eight squamous cell carcinomas, and eight erythroplakias with epithelial dysplasia. Twenty oral lesions without histological evidence of malignancy (13 lichen planus lesions...

  14. Solid phase measurements of antibody and lectin binding to xenogenic carbohydrate antigens

    DEFF Research Database (Denmark)

    Kirkeby, Svend; André, Sabine; Gabius, Hans-Joachim

    2004-01-01

    -Galalpha1 antibodies that both have been raised against glycans on rabbit red blood cells may recognize Galalpha-antigens with varying specificities. Binding results obtained after digestion with alpha-galactosidase indicate that some xenoreactive Galalpha groups are not directly accessible for removal......OBJECTIVES: In future pig-to-man xenotransplantation it is important to master tools that identify potentially xenogenic alphagalactose (Galalpha) antigens in the doner tissue. DESIGN AND METHODS: We have measured the binding potentials of Galalpha detecting lectins and antibodies, including...... and neoglycoproteins were treated with alpha-galactosidase and subsequently incubated with antibodies and lectins. The enzyme treatment was more deleterious on antibody binding than on lectin binding. CONCLUSION: Antibodies and lectins may bind to different galactose determinants on the glycoproteins. Two anti...

  15. Entirely Carbohydrate-Based Vaccines: An Emerging Field for Specific and Selective Immune Responses

    Science.gov (United States)

    Nishat, Sharmeen; Andreana, Peter R.

    2016-01-01

    Carbohydrates are regarded as promising targets for vaccine development against infectious disease because cell surface glycans on many infectious agents are attributed to playing an important role in pathogenesis. In addition, oncogenic transformation of normal cells, in many cases, is associated with aberrant glycosylation of the cell surface glycan generating tumor associated carbohydrate antigens (TACAs). Technological advances in glycobiology have added a new dimension to immunotherapy when considering carbohydrates as key targets in developing safe and effective vaccines to combat cancer, bacterial infections, viral infections, etc. Many consider effective vaccines induce T-cell dependent immunity with satisfactory levels of immunological memory that preclude recurrence. Unfortunately, carbohydrates alone are poorly immunogenic as they do not bind strongly to the MHCII complex and thus fail to elicit T-cell immunity. To increase immunogenicity, carbohydrates have been conjugated to carrier proteins, which sometimes can impede carbohydrate specific immunity as peptide-based immune responses can negate antibodies directed at the targeted carbohydrate antigens. To overcome many challenges in using carbohydrate-based vaccine design and development approaches targeting cancer and other diseases, zwitterionic polysaccharides (ZPSs), isolated from the capsule of commensal anaerobic bacteria, will be discussed as promising carriers of carbohydrate antigens to achieve desired immunological responses. PMID:27213458

  16. Entirely Carbohydrate-Based Vaccines: An Emerging Field for Specific and Selective Immune Responses

    Directory of Open Access Journals (Sweden)

    Sharmeen Nishat

    2016-05-01

    Full Text Available Carbohydrates are regarded as promising targets for vaccine development against infectious disease because cell surface glycans on many infectious agents are attributed to playing an important role in pathogenesis. In addition, oncogenic transformation of normal cells, in many cases, is associated with aberrant glycosylation of the cell surface glycan generating tumor associated carbohydrate antigens (TACAs. Technological advances in glycobiology have added a new dimension to immunotherapy when considering carbohydrates as key targets in developing safe and effective vaccines to combat cancer, bacterial infections, viral infections, etc. Many consider effective vaccines induce T-cell dependent immunity with satisfactory levels of immunological memory that preclude recurrence. Unfortunately, carbohydrates alone are poorly immunogenic as they do not bind strongly to the MHCII complex and thus fail to elicit T-cell immunity. To increase immunogenicity, carbohydrates have been conjugated to carrier proteins, which sometimes can impede carbohydrate specific immunity as peptide-based immune responses can negate antibodies directed at the targeted carbohydrate antigens. To overcome many challenges in using carbohydrate-based vaccine design and development approaches targeting cancer and other diseases, zwitterionic polysaccharides (ZPSs, isolated from the capsule of commensal anaerobic bacteria, will be discussed as promising carriers of carbohydrate antigens to achieve desired immunological responses.

  17. Intraspecific epitopic variation in a carbohydrate antigen exposed on the surface of Trichostrongylus colubriformis infective L3 larvae.

    Directory of Open Access Journals (Sweden)

    David R Maass

    2009-09-01

    Full Text Available The carbohydrate larval antigen, CarLA, is present on the exposed surface of all strongylid nematode infective L3 larvae tested, and antibodies against CarLA can promote rapid immune rejection of incoming Trichostrongylus colubriformis larvae in sheep. A library of ovine recombinant single chain Fv (scFv antibody fragments, displayed on phage, was prepared from B cell mRNA of field-immune sheep. Phage displaying scFvs that bind to the surface of living exsheathed T. colubriformis L3 larvae were identified, and the majority of worm-binding scFvs recognized CarLA. Characterization of greater than 500 worm surface binding phage resulted in the identification of nine different anti-CarLA scFvs that recognized three distinct T. colubriformis CarLA epitopes based on blocking and additive ELISA. All anti-CarLA scFvs were specific to the T. colubriformis species of nematode. Each of the three scFv epitope classes displayed identical Western blot recognition patterns and recognized the exposed surface of living T. colubriformis exsheathed L3 larvae. Surprisingly, each of the anti-CarLA scFvs was able to bind to only a subset of worms. Double-labelling indirect immunofluorescence revealed that the three classes of anti-CarLA scFvs recognize distinct, non-overlapping, T. colubriformis sub-populations. These results demonstrate that individual T. colubriformis L3 larvae display only one of at least three distinct antigenic forms of CarLA on their surface at any given time, and suggest that antigenic variation within CarLA is likely a mechanism of immune evasion in strongylid nematodes.

  18. Measurement of serum carcinoembryonic antigen, carbohydrate antigen 19-9, cytokeratin-19 fragment and matrix metalloproteinase-7 for detecting cholangiocarcinoma: a preliminary case-control study.

    Science.gov (United States)

    Lumachi, Franco; Lo Re, Giovanni; Tozzoli, Renato; D'Aurizio, Federica; Facomer, Flavio; Chiara, Giordano B; Basso, Stefano M M

    2014-11-01

    Cholangiocarcinoma is a malignant tumor of the liver arising from the bile duct epithelium, accounting for 10-25% of all primary hepatic cancers. The clinical presentation of this tumor is not specific and the diagnosis of early cholangiocarcinoma is difficult, especially in patients with other biliary diseases. Measurement of serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) are commonly used to monitor response to therapy, but are also useful for confirming the presence of a cholangiocarcinoma. In this setting, other biomarkers have been previously tested, including cytokeratin-19 fragment (CYFRA 21-1) and the matrix metalloproteinase-7 (MMP7). The purpose of this retrospective study was to determine the clinical usefulness of the assay of serum CEA, CA 19-9, CYFRA 21-1 and MMP7, individually and together, as tumor markers for the diagnosis of cholangiocarcinoma. Twenty-four patients (14 men, 10 women, 62.6±8.2 years of age) with histologically-confirmed cholangiocarcinoma (cases) and 25 age- and sex-matched patients with benign liver disease (controls) underwent measurement of these biomarkers. The mean values of all serum markers of patients with cholangiocarcinoma were significantly higher (pCYFRA 21-1: 76%, 79% and 78%; MMP7: 78%, 77% and 80%, respectively. The combination of all serum markers afforded 92.0% sensitivity and 96% specificity in detecting cholangiocarcinoma, showing the highest diagnostic accuracy (94%). In conclusion, our preliminary results suggest that the measurement of all four biomarkers together can help in the early detection of cholangiocarcinoma. PMID:25368272

  19. Simple mucin-type Tn and sialosyl-Tn carbohydrate antigens in salivary gland carcinomas

    DEFF Research Database (Denmark)

    Therkildsen, M H; Mandel, U; Christensen, M;

    1993-01-01

    -Tn, which are normally cryptic in human cells and secretions, including saliva and salivary glands. METHODS: Paraffin sections from 50 salivary gland carcinomas of different histologic types were investigated with immunohistologic studies and a panel of monoclonal antibodies with well-defined specificity...... for Tn and sialosyl-Tn. RESULTS: Tn and sialosyl-Tn antigens were expressed in the cytoplasm of glandular differentiated cells; in the luminal membranes and mucinous content of the glandular differentiated areas in almost all mucoepidermoid carcinomas and adenocarcinomas; and in carcinoma in pleomorphic...... adenoma, when the malignant component was an adenocarcinoma. In contrast, acinic cell carcinomas and adenoid cystic carcinomas expressed only minimal amounts of Tn and sialosyl-Tn, and the staining was seen only in relation to the luminal membrane and mucin of a few glandular structures. CONCLUSIONS...

  20. Antibody responses to a spore carbohydrate antigen as a marker of nonfatal inhalation anthrax in rhesus macaques.

    Science.gov (United States)

    Saile, Elke; Boons, Geert-Jan; Buskas, Therese; Carlson, Russell W; Kannenberg, Elmar L; Barr, John R; Boyer, Anne E; Gallegos-Candela, Maribel; Quinn, Conrad P

    2011-05-01

    The Bacillus anthracis exosporium protein BclA contains an O-linked antigenic tetrasaccharide whose terminal sugar is known as anthrose (J. M. Daubenspeck et al., J. Biol. Chem. 279:30945-30953, 2004). We hypothesized that serologic responses to anthrose may have diagnostic value in confirming exposure to aerosolized B. anthracis. We evaluated the serologic responses to a synthetic anthrose-containing trisaccharide (ATS) in a group of five rhesus macaques that survived inhalation anthrax following exposure to B. anthracis Ames spores. Two of five animals (RM2 and RM3) were treated with ciprofloxacin starting at 48 hours postexposure and two (RM4 and RM5) at 72 h postexposure; one animal (RM1) was untreated. Infection was confirmed by blood culture and detection of anthrax toxin lethal factor (LF) in plasma. Anti-ATS IgG responses were determined at 14, 21, 28, and 35 days postexposure, with preexposure serum as a control. All animals, irrespective of ciprofloxacin treatment, mounted a specific, measurable anti-ATS IgG response. The earliest detectable responses were on days 14 (RM1, RM2, and RM5), 21 (RM4), and 28 (RM3). Specificity of the anti-ATS responses was demonstrated by competitive-inhibition enzyme immunoassay (CIEIA), in which a 2-fold (wt/wt) excess of carbohydrate in a bovine serum albumin (BSA) conjugate of the oligosaccharide (ATS-BSA) effected >94% inhibition, whereas a structural analog lacking the 3-hydroxy-3-methyl-butyryl moiety at the C-4" of the anthrosyl residue had no inhibition activity. These data suggest that anti-ATS antibody responses may be used to identify aerosol exposure to B. anthracis spores. The anti-ATS antibody responses were detectable during administration of ciprofloxacin. PMID:21389148

  1. Microplate chemiluminescence enzyme immunoassay for the quantitative evaluation of carbohydrate antigen 72-4 in human serum

    Institute of Scientific and Technical Information of China (English)

    JIN Hui; WANG Xu; XIN TianBing; GAO Peng; LIN JinMing; LIANG ShuXuan

    2008-01-01

    A highly sensitive and specific microplate chemiluminescence enzyme immunoassay (CLEIA) was de-veloped for the quantitative evaluation of carbohydrate antigen 72-4 (CA72-4) in human serum, using luminol-H2O2 catalyzed by horseradish peroxidase (HRP) as the chemiluminescence system. The sim-ple and quick determination was accomplished through a sandwich reaction mode. Several physico-chemical parameters of the immunoreaction, including incubation conditions, antibody coating condi-tions, dilution ratio of anti-CA72-4-HRP conjugate, and chemiluminescence reaction time, were studied and optimized. The proposed method exhibited a linear range of 0-200 U/mL with correlation coeffi-cient and detection limit of 0.9995 and 0.18 U/mL, respectively. The inter-assay and intra-assay coeffi-cients of variation (CV) were both less than 10%. The average recovery of two clinical sera with low and high concentration CA72-4 was 99.3% and 98.7%, respectively. Normal tumor markers, including AFP, CEA, CA2.4-2, CA19-9 and CA15-3, did not cross-react with each other. The method's stability was evaluated by assessing its analytical performance after storing the immunoreagents at 4℃ and 37℃ for 7 days. Little difference was found, indicating satisfactory stability of the method. The present method has been successfully applied to the detection of CA72-4 human serum, and showed a good correlation with the commercially available ELISA kit (r2=0.9383). This method showed great potential in the fabrication of diagnostic kit for CA72-4, and could be well used in diagnosis of cancer in clinical practice.

  2. CdSe/ZnS Quantum Dot-Labeled Lateral Flow Strips for Rapid and Quantitative Detection of Gastric Cancer Carbohydrate Antigen 72-4

    OpenAIRE

    Yan, Xinyu; Wang, Kan; Lu, Wenting; Qin, Weijian; Cui, Daxiang; He, Jinghua

    2016-01-01

    Carbohydrate antigen 72-4 (CA72-4) is an important biomarker associated closely with diagnosis and prognosis of early gastric cancer. How to realize quick, sensitive, specific, and quantitative detection of CA72-4 in clinical specimens has become a great requirement. Herein, we reported a CdSe/ZnS quantum dot-labeled lateral flow test strip combined with a charge-coupled device (CCD)-based reader was developed for rapid, sensitive, and quantitative detection of CA72-4. Two mouse monoclonal an...

  3. Clinical significance of serum carbohydrate antigen 19-9 and its relationship with blood glucose in patients with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    武秀玲

    2013-01-01

    Objective To study the relationship between serum carbohydrate antigen 19-9 (CA19-9) and blood glucose level in patients with type 2 diabetes (T2DM) .Methods Totally 784 T2DM patients and 197 healthy controls were enrolled in this study.Age,duration,body mass index (BMI) ,systolic blood pressure (SBP) ,diastolic blood pressure (DBP) ,levels of fasting blood glucose (FBG) ,postprandial blood glucose (PBG) ,hemoglobin A1c (HbA1c) ,total cholesterol (TC) ,triglyceride (TG) ,

  4. Carbohydrates as allergens.

    Science.gov (United States)

    Commins, Scott P

    2015-01-01

    Complex carbohydrates are effective inducers of Th2 responses, and carbohydrate antigens can stimulate the production of glycan-specific antibodies. In instances where the antigen exposure occurs through the skin, the resulting antibody production can contain IgE class antibody. The glycan-stimulated IgE may be non-specific but may also be antigen specific. This review focuses on the production of cross-reactive carbohydrate determinants, the recently identified IgE antibody response to a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal), as well as discusses practical implications of carbohydrates in allergy. In addition, the biological effects of carbohydrate antigens are reviewed in setting of receptors and host recognition.

  5. Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes.

    Science.gov (United States)

    Liao, Shih-Fen; Liang, Chi-Hui; Ho, Ming-Yi; Hsu, Tsui-Ling; Tsai, Tsung-I; Hsieh, Yves S-Y; Tsai, Chih-Ming; Li, Shiou-Ting; Cheng, Yang-Yu; Tsao, Shu-Ming; Lin, Tung-Yi; Lin, Zong-Yan; Yang, Wen-Bin; Ren, Chien-Tai; Lin, Kuo-I; Khoo, Kay-Hooi; Lin, Chun-Hung; Hsu, Hsien-Yeh; Wu, Chung-Yi; Wong, Chi-Huey

    2013-08-20

    Carbohydrate-based vaccines have shown therapeutic efficacy for infectious disease and cancer. The mushroom Ganoderma lucidum (Reishi) containing complex polysaccharides has been used as antitumor supplement, but the mechanism of immune response has rarely been studied. Here, we show that the mice immunized with a l-fucose (Fuc)-enriched Reishi polysaccharide fraction (designated as FMS) induce antibodies against murine Lewis lung carcinoma cells, with increased antibody-mediated cytotoxicity and reduced production of tumor-associated inflammatory mediators (in particular, monocyte chemoattractant protein-1). The mice showed a significant increase in the peritoneal B1 B-cell population, suggesting FMS-mediated anti-glycan IgM production. Furthermore, the glycan microarray analysis of FMS-induced antisera displayed a high specificity toward tumor-associated glycans, with the antigenic structure located in the nonreducing termini (i.e., Fucα1-2Galβ1-3GalNAc-R, where Gal, GalNAc, and R represent, respectively, D-galactose, D-N-acetyl galactosamine, and reducing end), typically found in Globo H and related tumor antigens. The composition of FMS contains mainly the backbone of 1,4-mannan and 1,6-α-galactan and through the Fucα1-2Gal, Fucα1-3/4Man, Fucα1-4Xyl, and Fucα1-2Fuc linkages (where Man and Xyl represent d-mannose and d-xylose, respectively), underlying the molecular basis of the FMS-induced IgM antibodies against tumor-specific glycans.

  6. Delayed radiation-induced inflammation accompanying a marked carbohydrate antigen 19-9 elevation in a patient with resected pancreatic cancer

    Science.gov (United States)

    Mattes, Malcolm D.; Cardinal, Jon S.; Jacobson, Geraldine M.

    2016-01-01

    Although carbohydrate antigen (CA) 19-9 is a useful tumor marker for pancreatic cancer, it can also become elevated from a variety of benign and malignant conditions. Herein we describe an unusual presentation of elevated CA 19-9 in an asymptomatic patient who had previously undergone adjuvant chemotherapy and radiation therapy for resected early stage pancreatic cancer. The rise in CA 19-9 might be due to delayed radiation-induced inflammation related to previous intra-abdominal radiation therapy with or without radiation recall induced by gemcitabine. After treatment with corticosteroids the CA 19-9 level decreased to normal, and the patient has not developed any evidence of recurrent cancer to date. PMID:27306770

  7. Antibody Responses to a Spore Carbohydrate Antigen as a Marker of Nonfatal Inhalation Anthrax in Rhesus Macaques ▿

    OpenAIRE

    Saile, Elke; Boons, Geert-Jan; Buskas, Therese; Carlson, Russell W.; Kannenberg, Elmar L; Barr, John R.; Boyer, Anne E.; Gallegos-Candela, Maribel; Quinn, Conrad P.

    2011-01-01

    The Bacillus anthracis exosporium protein BclA contains an O-linked antigenic tetrasaccharide whose terminal sugar is known as anthrose (J. M. Daubenspeck et al., J. Biol. Chem. 279:30945–30953, 2004). We hypothesized that serologic responses to anthrose may have diagnostic value in confirming exposure to aerosolized B. anthracis. We evaluated the serologic responses to a synthetic anthrose-containing trisaccharide (ATS) in a group of five rhesus macaques that survived inhalation anthrax foll...

  8. Amperometric carbohydrate antigen 19-9 immunosensor based on three dimensional ordered macroporous magnetic Au film coupling direct electrochemistry of horseradish peroxidase

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qi [College of Sciences, Nanjing Tech University, Nanjing 211816 (China); Chen, Xiaojun, E-mail: chenxj_njut@126.com [College of Sciences, Nanjing Tech University, Nanjing 211816 (China); State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, Nanjing 210009 (China); Tang, Yin [Zhangjiagang Hospital of Traditional Chinese Medicine, Zhangjiagang 215600 (China); Ge, Lingna; Guo, Buhua [College of Sciences, Nanjing Tech University, Nanjing 211816 (China); Yao, Cheng, E-mail: yaochengnjut@163.com [College of Sciences, Nanjing Tech University, Nanjing 211816 (China)

    2014-03-01

    Highlights: • Three dimensional ordered macroporous magnetic electrode was newly used in electrochemical immunosensor. • The large surface area of macroporous magnetic electrode could improve the immobilized amount of antibody. • Au nanoparticles functionalized SBA-15 was used to immobilize enzyme labeled Ab₂ and enzyme. • Macroporous magnetic electrode and Au nanoparticles composite facilitated the direct electron transfer of enzyme. • The immunoassay avoided adding electron transfer mediator, simplifying the procedure. Abstract: A sandwich-type electrochemical immunosensor for the detection of carbohydrate antigen 19-9 (CA 19-9) antigen based on the immobilization of primary antibody (Ab₁) on three dimensional ordered macroporous magnetic (3DOMM) electrode, and the direct electrochemistry of horseradish peroxidase (HRP) that was used as both the label of secondary antibody (Ab₂) and the blocking reagent. The 3DOMM electrode was fabricated by introducing core–shell Au–SiO₂@Fe₃O₄ nanospheres onto the surface of three dimensional ordered macroporous (3DOM) Au electrode via the application of an external magnet. Au nanoparticles functionalized SBA-15 (Au@SBA-15) was conjugated to the HRP labeled secondary antibody (HRP-Ab₂) through the Au–SH or Au–NH₃⁺ interaction, and HRP was also used as the block reagent. The formation of antigen–antibody complex made the combination of Au@SBA-15 and 3DOMM exhibit remarkable synergistic effects for accelerating direct electron transfer (DET) between HRP and the electrode. Under the optimal conditions, the DET current signal increased proportionally to CA 19-9 concentration in the range of 0.05 to 15.65 U mL⁻¹ with a detection limit of 0.01 U mL⁻¹. Moreover, the immunosensor showed high selectivity, good stability, satisfactory reproducibility and regeneration. Importantly, the developed method was used to assay clinical serum specimens, achieving a good relation with those obtained from

  9. Pretreatment Carbohydrate Antigen 19-9 Level Indicates Tumor Response, Early Distant Metastasis, Overall Survival, and Therapeutic Selection in Localized and Unresectable Pancreatic Cancer

    International Nuclear Information System (INIS)

    Purpose: The use of chemoradiotherapy (CRT) for localized and unresectable pancreatic cancer has been disputed because of high probability of distant metastasis. Thus, we analyzed the effect of clinical parameters on tumor response, early distant metastasis within 3 months (DM3m), and overall survival to identify an indicator for selecting patients who would benefit from CRT. Methods and Materials: This study retrospectively analyzed the data from 84 patients with localized and unresectable pancreatic cancer who underwent CRT between August 2002 and October 2009. Sex, age, tumor size, histological differentiation, N classification, pre- and post-treatment carbohydrate antigen (CA) 19-9 level, and CA 19-9 percent decrease were analyzed to identify risk factors associated with tumor response, DM3m, and overall survival. Results: For all 84 patients, the median survival time was 12.5 months (range, 2–31.9 months), objective response (complete response or partial response) to CRT was observed in 28 patients (33.3%), and DM3m occurred in 24 patients (28.6%). Multivariate analysis showed that pretreatment CA 19-9 level (≤400 vs. >400 U/ml) was significantly associated with tumor response (45.1% vs. 15.2%), DM3m (19.6% vs. 42.4%), and median overall survival time (15.1 vs. 9.7 months) (p 3m, and overall survival and identifying patients who will benefit from CRT.

  10. Novel redox species polyaniline derivative-Au/Pt as sensing platform for label-free electrochemical immunoassay of carbohydrate antigen 199.

    Science.gov (United States)

    Wang, Liyuan; Shan, Jiao; Feng, Feng; Ma, Zhanfang

    2016-03-10

    A novel electrochemical redox-active nanocomposite was synthesized by a one-pot method using N,N'-diphenyl-p-phenylediamine as monomer, and HAuCl4 and K2PtCl4 as co-oxidizing agents. The as-prepared poly(N,N'-diphenyl-p-phenylediamine)-Au/Pt exhibited admirable electrochemical redox activity at 0.15 V, excellent H2O2 electrocatalytic ability and favorable electron transfer ability. Based on these, the evaluation of the composite as sensing substrate for label-free electrochemical immunosensing to the sensitive detection of carbohydrate antigen 199 was described. This technique proved to be a prospective detection tool with a wide liner range from 0.001 U mL(-1) to 40 U mL(-1), and a low detection limit of 2.3 × 10(-4) U mL(-1) (S/N = 3). In addition, this method was used for the analysis of human serum sample, and good agreement was obtained between the values and those of enzyme-linked immunosorbent assay, implying the potential application in clinical research. Importantly, the strategy of the present substrate could be extended to other polymer-based nanocomposites such as polypyrrole derivatives or polythiophene derivatives, and this could be of great significance for the electrochemical immunoassay.

  11. Aire-dependent thymic development of tumor-associated regulatory T cells*

    Science.gov (United States)

    Malchow, Sven; Leventhal, Daniel S.; Nishi, Saki; Fischer, Benjamin I.; Shen, Lynn; Paner, Gladell P.; Amit, Ayelet S.; Kang, Chulho; Geddes, Jenna E.; Allison, James P.; Socci, Nicholas D.; Savage, Peter A.

    2013-01-01

    Despite considerable interest in the modulation of tumor-associated Foxp3+ regulatory T cells (Tregs) for therapeutic benefit, little is known about the developmental origins of these cells and the nature of the antigens that they recognize. Here, we identified an endogenous population of antigen-specific Tregs (termed “MJ23” Tregs) found recurrently enriched in the tumors of mice with oncogene-driven prostate cancer. MJ23 Tregs were not reactive to a tumor-specific antigen, but instead recognized a prostate-associated antigen that was present in tumor-free mice. MJ23 Tregs underwent Aire-dependent thymic development in both male and female mice. Thus Aire-mediated expression of peripheral tissue antigens drives the thymic development of a subset of organ-specific Tregs, which are likely co-opted by tumors developing within the associated organ. PMID:23471412

  12. A novel sandwich electrochemiluminescence immunosensor for ultrasensitive detection of carbohydrate antigen 19-9 based on immobilizing luminol on Ag@BSA core/shell microspheres.

    Science.gov (United States)

    Zhang, Amin; Xiang, Hongkun; Zhang, Xin; Guo, Weiwei; Yuan, Enhui; Huang, Chusen; Jia, Nengqin

    2016-01-15

    A novel sandwich-type electrochemiluminescence immunosensor based on immobilizing luminol on Ag@BSA core/shell microspheres (Ag@BSA-luminol) for ultrasensitive detection of tumor marker carbohydrate antigen 19-9 (CA19-9) has been developed. Herein, magnetic carbon nanotubes (MAGCNTs) decorated with polyethylenimine (PEI) was used to construct the base of the immunosensor. MAGCNTs with prominent electrical conductivity and high surface area could be beneficial for promoting the electron transfer and loading plenty of primary antibodies (Ab1) via glutaraldehyde (GA). Meanwhile, the magnetic property of MAGCNTs makes it easy to be attached to the surface of magnetic glass carbon electrode (MGCE) through magnetism interaction, which provides an outstanding platform for this immunosensor. Moreover, Ag@BSA microspheres with large surface area, good stability, and excellent biocompatibility were desirable candidates for effective cross-link of CA19-9 detection antibodies (Ab2). A more interesting thing was that ELISA color reaction was used as an ultrasensitive strategy for identifying Ab2 was successfully coated on Ag@BSA with the naked eye. Additionally, we immobilized the luminol on the surface of Ag@BSA to prepare the target immunosensor. Immobilization of luminol on the surface of Ag@BSA could decrease the distance between luminophores and the electrode surface, leading to great enhancement of the ECL intensity of luminol in the present of hydrogen peroxide (H2O2). Under the optimal conditions, the intensity of the ECL immunosensor increased linearly with the logarithm of CA19-9 concentration in a wide linear range from 0.0005 to 150UmL(-1) with a detection limit of 0.0002UmL(-1) (S/N=3). All the results suggested the prepared CA19-9 immunosensor displayed high sensitivity, excellent stability and good specificity. The developed method opened a new avenue to clinical bioassay.

  13. CdSe/ZnS Quantum Dot-Labeled Lateral Flow Strips for Rapid and Quantitative Detection of Gastric Cancer Carbohydrate Antigen 72-4

    Science.gov (United States)

    Yan, Xinyu; Wang, Kan; Lu, Wenting; Qin, Weijian; Cui, Daxiang; He, Jinghua

    2016-03-01

    Carbohydrate antigen 72-4 (CA72-4) is an important biomarker associated closely with diagnosis and prognosis of early gastric cancer. How to realize quick, sensitive, specific, and quantitative detection of CA72-4 in clinical specimens has become a great requirement. Herein, we reported a CdSe/ZnS quantum dot-labeled lateral flow test strip combined with a charge-coupled device (CCD)-based reader was developed for rapid, sensitive, and quantitative detection of CA72-4. Two mouse monoclonal antibodies (mAbs) against CA72-4 were employed. One of them was coated as a test line, while another mAb was labeled with quantum dots and coated onto conjugate pad. The goat anti-mouse IgG was immobilized as a control line. After sample was added, a sandwich structure was formed with CA72-4 and these two mAbs. The fluorescent signal from quantum dots (QD)-labeled mAb in sandwich structure was related to the amount of detected CA72-4. A CCD-based reader was used to realize quantitative detection of CA72-4. Results showed that developed QD-labeled lateral flow strips to detect CA72-4 biomarker with the sensitivity of 2 IU/mL and 10 min detection time. One hundred sera samples from clinical patients with gastric cancer and healthy people were used to confirm specificity of this strip method; results showed that established strip method own 100 % reproducibility and 100 % specificity compared with Roche electrochemiluminescence assay results. In conclusion, CdSe/ZnS quantum dot-labeled lateral flow strips for detection of CA72-4 could realize rapid, sensitive, and specific detection of clinical samples and could own great potential in clinical translation in near future.

  14. CdSe/ZnS Quantum Dot-Labeled Lateral Flow Strips for Rapid and Quantitative Detection of Gastric Cancer Carbohydrate Antigen 72-4.

    Science.gov (United States)

    Yan, Xinyu; Wang, Kan; Lu, Wenting; Qin, Weijian; Cui, Daxiang; He, Jinghua

    2016-12-01

    Carbohydrate antigen 72-4 (CA72-4) is an important biomarker associated closely with diagnosis and prognosis of early gastric cancer. How to realize quick, sensitive, specific, and quantitative detection of CA72-4 in clinical specimens has become a great requirement. Herein, we reported a CdSe/ZnS quantum dot-labeled lateral flow test strip combined with a charge-coupled device (CCD)-based reader was developed for rapid, sensitive, and quantitative detection of CA72-4. Two mouse monoclonal antibodies (mAbs) against CA72-4 were employed. One of them was coated as a test line, while another mAb was labeled with quantum dots and coated onto conjugate pad. The goat anti-mouse IgG was immobilized as a control line. After sample was added, a sandwich structure was formed with CA72-4 and these two mAbs. The fluorescent signal from quantum dots (QD)-labeled mAb in sandwich structure was related to the amount of detected CA72-4. A CCD-based reader was used to realize quantitative detection of CA72-4. Results showed that developed QD-labeled lateral flow strips to detect CA72-4 biomarker with the sensitivity of 2 IU/mL and 10 min detection time. One hundred sera samples from clinical patients with gastric cancer and healthy people were used to confirm specificity of this strip method; results showed that established strip method own 100 % reproducibility and 100 % specificity compared with Roche electrochemiluminescence assay results. In conclusion, CdSe/ZnS quantum dot-labeled lateral flow strips for detection of CA72-4 could realize rapid, sensitive, and specific detection of clinical samples and could own great potential in clinical translation in near future. PMID:26969591

  15. Silver-functionalized g-C3N4 nanohybrids as signal-transduction tags for electrochemical immunoassay of human carbohydrate antigen 19-9.

    Science.gov (United States)

    Sun, Ai-Li; Qi, Qing-An

    2016-07-21

    A simple and feasible electrochemical immunosensing platform was developed for highly efficient screening of a disease-related protein (human carbohydrate antigen 19-9, CA 19-9 used in this case) using silver-functionalized g-C3N4 nanosheets (Ag/g-C3N4) as signal-transduction tags. Initially, Ag/g-C3N4 nanohybrids were synthesized by combining thermal polymerization of the melamine precursor with the photo-assisted reduction method. Thereafter, the as-synthesized Ag/g-C3N4 nanohybrids were utilized for the labeling of the anti-CA 19-9 detection antibody by using a typical carbodiimide coupling method. The assay was carried out on a capture antibody-modified glassy carbon electrode in a sandwich-type detection mode. The detectable signal mainly derived from the voltammetric characteristics of the immobilized nanosilver particles on the g-C3N4 nanosheets within the applied potentials. Under the optimal conditions, the voltammetric peak currents increased with the increasing amount of target CA 19-9, and exhibited a wide linear range from 5.0 mU mL(-1) to 50 U mL(-1) with a detection limit of 1.2 mU mL(-1). Our strategy also displayed good reproducibility, precision and specificity. The results of the analysis of clinical serum specimens were in good accordance with the results obtained by an enzyme-linked immunosorbent assay (ELISA) method. The newly developed immunosensing system is promising for enzyme-free and cost-effective analysis of low-abundance proteins. PMID:27183220

  16. Rapid detection and quantification of tumor marker carbohydrate antigen 72-4 (CA72-4) using a superparamagnetic immunochromatographic strip.

    Science.gov (United States)

    Chen, Yanrong; Wang, Kan; Liu, Zongrui; Sun, Rongjin; Cui, Daxiang; He, Jinghua

    2016-03-01

    Rapid and quantitative detection of biomarkers with high sensitivity and specificity has become a common practice in the clinical diagnosis and treatment of cancer. Herein, a quantitative lateral flow immunoassay (LFIA) based on superparamagnetic nanoparticles (SPMNPs) was developed for detection of carbohydrate antigen 72-4 (CA72-4) in human serum. This direct and rapid method did not involve any sample preparation and was accomplished using a test strip in which a sandwich reaction was performed. Probes on the conjugate pad were prepared by coupling monoclonal antibody CC49 specific to CA72-4 onto SPMNPs. Coupled monoclonal antibody B72.3 and goat anti-mouse IgG were loaded onto a nitrocellulose (NC) membrane, serving as the test and control lines, respectively. Initially, results were evaluated by macroscopic observation. Afterwards, the magnetic signal strength of the reaction area was quantified using a magnetic assay reader (MAR). Several parameters that may influence the detection sensitivity were studied and optimized. Under optimal conditions, the proposed method was capable of detecting as low as 0.38 IU/mL of CA72-4 in 20 min and had a wide detection linearity range (0-100 IU/mL). We evaluated 100 clinical samples (70 positive and 30 negative) to assess the validity of these test strips, which exhibited high sensitivity (99 %) and specificity (97 %). The results indicated a high rate of accuracy (98.4-102 %) and a low relative standard deviation according to the average recovery test. In conclusion, the test strips based on SPMNP probes are a rapid, sensitive, and quantitative method for the detection of CA72-4 and possess great potential in point-of-care testing (POCT). Graphical Abstract Schematic illustration of the strategy for CA72-4 detection and quantification using a superparamagnetic immunochromatographic strip. PMID:26825343

  17. Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

    Energy Technology Data Exchange (ETDEWEB)

    Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas, E-mail: tke@uams.edu [Winthrop P. Rockefeller Cancer Institute and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

    2011-11-11

    Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses.

  18. Counting carbohydrates

    Science.gov (United States)

    Carb counting; Carbohydrate-controlled diet; Diabetic diet; Diabetes-counting carbohydrates ... goal is not to limit carbohydrates in the diet completely, but to make ... with diabetes can better control their blood sugar if they ...

  19. 血清CA125、CEA水平与宫颈癌相关性分析%Association of serum carcinoembryonic antigen and carbohydrate antigen 125 with cervical cancer

    Institute of Scientific and Technical Information of China (English)

    胡跃华

    2012-01-01

    Objective To analyze the association of serum carcinoembryonic antigen ( CEA )and carbohydrate antigen 125 ( CA125 ) with cervical cancer.Methods 100 patients with cervical cancer who had been treated in our hospital during the period of February 2007 to March 2011 were enrolled into a study group.Serum levels of CEA and CA125 were detected and their assoication with cervical cancer was analyzed; and the levels of these markers were compared with those from 60 non-cervical cancer patients ( control group ).Results Serum levels of CEA and CA125 were higher in the study group than in the control group,with a significant difference between 2 groups ( P< 0.05 ) except for stage Ⅰ cervical cancer.The correlation between CA125 and stages of cervical cancer was greater than that between CEA and cervical cancer ( P< 0.05 ).Conclusions Serum levels of CEA and CA125 are associated with cervical cancer at some degree.CA125 has more diagnostic values than CEA.%目的 分析研究血清CA125(糖链抗原125)、CEA(癌胚抗原)水平与宫颈癌的相关性.方法 将我院从2007年2月至2011年3月收治的100例宫颈癌病患设为实验组,进行血清CA125、CEA水平检测,并与宫颈癌分期相分析,将同期收治的60例非宫颈癌病患设为对照组,对比两组血清CA125、CEA水平.结果 实验组血清CA125、CEA水平均高于对照组,除Ⅰ期宫颈癌数据外,差异有统计学意义(P<0.05);血清CA125与宫颈癌分期的相关性高于血清CEA,差异有统计学意义(P<0.05 ).结论 血清CA125、CEA水平与宫颈癌有一定相关性,检测简单方便,且血清CA125比血清CEA更具诊断价值.

  20. Endocrine tumors associated with the vagusnerve

    Science.gov (United States)

    Varoquaux, Arthur; Kebebew, Electron; Sebag, Fréderic; Wolf, Katherine; Henry, Jean-François; Pacak, Karel; Taïeb, David

    2016-01-01

    The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of an endocrine tumor associated with the vagus nerve. This rare, neural-crest tumor constitutes the second most common site of hereditary head and neck paragangliomas (HNPGLs), most often in relation to mutations in the succinate dehydrogenase subunit D (SDHD) gene. The treatment paradigm for VPGL has progressively shifted from surgery to abstention or therapeutic radiation with curative-like outcomes. Parathyroid tissue and parathyroid adenoma can also be found in close association with the vagus nerve in intra or paravagal situations. Vagal parathyroid adenoma can be identified with preoperative imaging or suspected intraoperatively by experienced surgeons. Vagal parathyroid adenomas located in the neck or superior mediastinum can be removed via initial cervicotomy, while those located in the aorto-pulmonary window require a thoracic approach. This review particularly emphasizes the embryology, molecular genetics, and modern imaging of these tumors. PMID:27406876

  1. Carbohydrate Analysis

    Science.gov (United States)

    Bemiller, James N.

    Carbohydrates are important in foods as a major source of energy, to impart crucial textural properties, and as dietary fiber which influences physiological processes. Digestible carbohydrates, which are converted into monosaccharides, which are absorbed, provide metabolic energy. Worldwide, carbohydrates account for more than 70% of the caloric value of the human diet. It is recommended that all persons should limit calories from fat (the other significant source) to not more than 30% and that most of the carbohydrate calories should come from starch. Nondigestible polysaccharides (all those other than starch) comprise the major portion of dietary fiber (Sect. 10.5). Carbohydrates also contribute other attributes, including bulk, body, viscosity, stability to emulsions and foams, water-holding capacity, freeze-thaw stability, browning, flavors, aromas, and a range of desirable textures (from crispness to smooth, soft gels). They also provide satiety. Basic carbohydrate structures, chemistry, and terminology can be found in references (1, 2).

  2. Carbohydrate Loading.

    Science.gov (United States)

    Csernus, Marilyn

    Carbohydrate loading is a frequently used technique to improve performance by altering an athlete's diet. The objective is to increase glycogen stored in muscles for use in prolonged strenuous exercise. For two to three days, the athlete consumes a diet that is low in carbohydrates and high in fat and protein while continuing to exercise and…

  3. Carbohydrate malabsorption

    DEFF Research Database (Denmark)

    Rumessen, J J; Nordgaard-Andersen, I; Gudmand-Høyer, E

    1994-01-01

    Previous studies in small series of healthy adults have suggested that parallel measurement of hydrogen and methane resulting from gut fermentation may improve the precision of quantitative estimates of carbohydrate malabsorption. Systematic, controlled studies of the role of simultaneous hydrogen...

  4. 糖类抗原检测在非小细胞肺癌诊疗中的应用%Application of the carbohydrate antigen detection for diagnosis and treatment in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    吴小进; 米燕燕; 胡安康; 王伟; 桑纯利; 冯苏梅; 殷咏梅; 鄂云祥

    2013-01-01

    目的 探讨糖类抗原检测用于非小细胞肺癌(NSCLC)诊疗的临床意义.方法 采用血清糖类抗原多肿瘤标志物蛋白芯片检测系统对已确诊的60例NSCLC患者的血清CA19-9、CA242、CA125和CA153水平进行检测,并与肺良性病变对照组和健康对照组进行比较.结果 肺癌组血清CA19-9、CA242、CA125和CA153的阳性检出率高于肺良性病变对照组和健康对照组,且3组血清CA19-9、CA125和CA153的差异尤为显著(P<0.05).肺腺癌患者血清CA19-9和CA125的阳性检出率高于肺鳞癌患者(P<0.05).NSCLC患者分期越晚,4种糖类抗原的阳性检出率越高,其中CA125和CA153在Ⅰ~Ⅱ期的阳性检出率分别为38.5%和30.8%,高于CA19-9和CA242的7.7%和7.7%(P<0.05).结论 糖类抗原检测在NSCLC诊疗方面具有较好的临床应用价值,可以作为诊断、分期及病程监测等方面常规检测方法的辅助手段.%Objective To explore the clinical significance of the carbohydrate antigen detection for diagnosis and treatment in non-small cell lung cancer(NSCLC). Methods The levels of serum CA19-9, CA242, CA125 and CA153 of 60 confirmed patients with NSCLC were measured by multiple tumor marker protein chip detection system and were compared with benign lung lesions control group and the healthy control group. Results The positive rate of serum CA19-9, CA242, CA125 and CA153 in the lung cancer group were higher than benign lung lesions control group and healthy control group, but there was particularly apparent difference in serum CA19-9, CA125 and CA153( P <0. 05). The positive rates of serum CA19-9 and CA125 in the patients with lung adenocarcinoma were significantly higher than those in patients with squamous cell carcinoma ( P <0. 05) . The positive rates of 4 carbohydrate antigens raised with clinical stages. The positive rates of CA125 and CA153 in stage I -II were 38. 5% and 30. 8% , which were higher than those of CA19-9 and CA242, with significant

  5. Highlights on FOX03 and tumor-associated dendritic cells in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Kwong Y Tsang; James L Gulley

    2011-01-01

    @@ Cancer immunotherapy sometimes fails to provoke effective immune responses because of immunosuppressive mechanisms present in the tumor-bearing host.Dendritic cells (DCs) are the most potent antigenpresenting cells.After internalizing tumorassociated antigens (TAAs) at the tumor site,CCR7+ DCs traffic to the tumor-draining lymph nodes,where they influence the maturation of T cells.DCs may also be present at the tumor site.These tumor-associated DCs (TADCs) cross-present TAAs to recruited CD8+ T cells,which develop into TAA-specific effector cells.When activated,TADCs can mediate the sensitization of naive T cells that have been recruited into the tumor site.For this reason,interaction between tumor-infiltrating T cells and TADCs is essential for activating and maintaining specific antitumor immune responses.

  6. Extra-Abdominal Desmoid Tumors Associated with Familial Adenomatous Polyposis

    Directory of Open Access Journals (Sweden)

    George T. Calvert

    2012-01-01

    Full Text Available Extra-abdominal desmoid tumors are a significant cause of morbidity in patients with familial adenomatous polyposis syndrome. Understanding of the basic biology and natural history of these tumors has increased substantially over the past decade. Accordingly, medical and surgical management of desmoid tumors has also evolved. This paper analyzes recent evidence pertaining to the epidemiology, molecular biology, histopathology, screening, and treatment of extra-abdominal desmoid tumors associated with familial adenomatous polyposis syndrome.

  7. Larynx carcinoma regulates tumor-associated macrophages through PLGF signaling

    OpenAIRE

    Xu Zhou(Key Laboratory of Optical Astronomy, National Astronomical Observatories, Chinese Academy of Sciences, Beijing, 100012, China); Ying Qi

    2015-01-01

    Cancer neovascularization plays an essential role in the metastasis of larynx carcinoma (LC). However, the underlying molecular mechanisms are not completely understood. Recently, we reported that placental growth factor (PLGF) regulates expression of matrix metalloproteinase 3 (MMP3) through ERK/MAPK signaling pathway in LC. Here, we show that MMP9 upregulated in LC, and appeared to be mainly produced by M2 macrophages (tumor-associated macrophages (TAM)). In a transwell co-culture system, P...

  8. Understanding Carbohydrates

    Science.gov (United States)

    ... Low-calorie sweeteners are also called artificial sweeteners, sugar substitutes or non-nutritive sweeteners. They can be used to sweeten food and drinks for less calories and carbohydrate when they replace sugar. Sugar and Desserts With diabetes, it's important to ...

  9. Effect of anticancer therapy on Tn antigen exposure on the leucocyte membranes in patients with leukemia

    Directory of Open Access Journals (Sweden)

    G. S. Maslak

    2014-08-01

    Full Text Available Tn-antigen (Thomsen-nouvelle antigen is tumor-associated carbohydrate antigen with only one GalNAc residue attached to serine or threonine of polypeptide chain. There is not enough data about the expression of this glycotope in hematologic processes. But the correlations between increasing Tn-antigen expression on the cell surface and tumor growth progression, invasion, and activation of cell migration are well known. Therefore, the currently important area of modern research is studying of the impact of anticancer therapy by expression of this carbohydrate antigen in the onco-proliferative process. There are two types of cytostatic therapies in clinical hospitals of Ukraine: COP-therapy (cyclophosphamide, vincristine, prednisone and FC-therapy (fludarabine, cyclophosphamide, which are the most popular due to their effectiveness and low price. The aim of our study was to investigate Tn-antigen exposure on the surface of lymphocytes, monocytes and granulocytes in polycythemia vera and subleukemic myelosis; to examine the influence of COP- and FC-therapies on Tn-antigen exponation in patients with chronic lymphocytic leukemia. The objects of the study were blood cells of patients with chronic lymphocytic leukemia (n = 25, polycythemia vera (n = 15 and subleukemic myelosis (n = 15 aged 58–66 years. Healthy hematologic volunteers (n = 15 aged 55 to 65 years were in the control group. Lymphocytes of patients with chronic lymphocytic leukemia (n = 25 were also studied after the chemotherapy treatment of patients divided into two groups: those who took COP-therapy (n = 13; and those who treated with FC-therapy (n = 12. Tn-antigen exposure on lymphocytes, monocytes and granulocytes was investigated by Beckman Сoulter EPICS flow cytometer with primary monoclonal Tn-antigen anybodies (Institute of Immunology, Moscow, Russia and secondary fluorescein isothiocyanate labeled antybodies (Millipore, USA. The number of dead cells was monitored by binding

  10. Immunotherapy for prostate cancer: lessons from responses to tumor-associated antigens

    NARCIS (Netherlands)

    Westdorp, H.; Skold, A.; Snijer, B.A.; Franik, S.; Mulder, S.F.; Major, P.P.; Foley, R.; Gerritsen, W.R.; Vries, I.J.M. de

    2014-01-01

    Prostate cancer (PCa) is the most common cancer in men and the second most common cause of cancer-related death in men. In recent years, novel therapeutic options for PCa have been developed and studied extensively in clinical trials. Sipuleucel-T is the first cell-based immunotherapeutic vaccine fo

  11. Tumor-associated antigens identified by mRNA expression profiling as tumor rejection epitopes

    DEFF Research Database (Denmark)

    Andersen, Marie; Ruhwald, Morten; Thorn, Mette;

    2003-01-01

    immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth. SM7 inoculated mice treated with a blocking antibody against the inhibitory T cell signal transducing molecule CTLA4 appeared to delay tumor take......Thirteen H-2b-binding peptides derived from six potentially overexpressed proteins in p53-/- thymoma (SM7) cells were studied for immunogenecity and vaccine-induced prevention of tumor growth in mice inoculated with SM7 tumor cells. Six of the peptides generated specific CTL responses after......, suggesting that SM7 thymoma cells are recognized by the adaptive immune system of the host. However, prophylactic vaccination with RAD23-31 and RAD24-31 peptides combined with anti-CTLA4 Ab treatment and did not improve tumor resistance. Our data would indicate that vaccination with immunogenic peptides...

  12. 75 FR 16490 - Prospective Grant of Exclusive License: Development of PANVAC and Tumor Associated Antigens as...

    Science.gov (United States)

    2010-04-01

    ...'') located in Mountain View, CA, USA. Intellectual Property: 1. U.S. Patent No. 6,756,038 issued June 29...; Group II--Nonexclusive Licensed Patent Rights: 1. U.S. Patent No. 6,969,609 issued November 29, 2005; U... counterparts . The patent rights in these inventions have been assigned to the United States of America....

  13. 78 FR 50425 - Prospective Grant of Exclusive License: Development of Brachyury Tumor Associated Antigens as...

    Science.gov (United States)

    2013-08-19

    .... Patents and Patent Applications to Bavarian Nordic Immunotherapeutics (``BNIT'') located in Mountain View... international applications, continuation applications and divisional applications. The patent rights in these... Rights for development of pox virus-based immunotherapeutics for colorectal cancer. DATES: Only...

  14. Tumor-associated antigens identified by mRNA expression profiling as tumor rejection epitopes

    DEFF Research Database (Denmark)

    Andersen, Marie Louise; Ruhwald, Morten; Thorn, Mette;

    2003-01-01

    immunization, but only two of these peptides (RAD23-31 and RAD24-31) were capable of generating a weak vaccination-induced protection against adoptive tumor growth. SM7 inoculated mice treated with a blocking antibody against the inhibitory T cell signal transducing molecule CTLA4 appeared to delay tumor take...... derived from potentially overexpressed tumor proteins, as identified by mRNA expression profiling of p53-/- thymoma cells, at best results in a weak tumor protection thus questioning this way of detection of new tumor rejection epitopes....

  15. Tumor-Associated Macrophages in Oncolytic Virotherapy: Friend or Foe?

    Directory of Open Access Journals (Sweden)

    Nicholas L. Denton

    2016-07-01

    Full Text Available Cancer therapy remains a challenge due to toxicity limitations of chemotherapy and radiation therapy. Oncolytic viruses that selectively replicate and destroy cancer cells are of increasing interest. In addition to direct cell lysis, these vectors stimulate an anti-tumor immune response. A key regulator of tumor immunity is the tumor-associated macrophage population. Macrophages can either support oncolytic virus therapy through pro-inflammatory stimulation of the anti-tumor response at the cost of hindering direct oncolysis or through immunosuppressive protection of virus replication at the cost of hindering the anti-tumor immune response. Despite similarities in macrophage interaction between adult and pediatric tumors and the abundance of research supporting macrophage modulation in adult tumors, there are few studies investigating macrophage modulation in pediatric cancers or modulation of immunotherapy. We review the current state of knowledge regarding macrophages in cancers and their influence on oncolytic virotherapy.

  16. Reciprocal Supportive Interplay between Glioblastoma and Tumor-Associated Macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Wenchao; Bao, Shideng, E-mail: baos@ccf.org [Department of Stem Cell Biology and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195 (United States)

    2014-03-26

    Glioblastoma multiforme (GBM) is the most lethal and aggressive type of primary brain malignancy. Failures of the traditional therapies in treating GBMs raise the urgent requirement to develop new approaches with more responsive targets. The phenomenon of the high infiltration of tumor-associated macrophages (TAMs) into GBMs has been observed for a long time. Regardless of the limited knowledge about TAMs, the high percentage of supportive TAM in GBM tumor mass makes it possible to be a good target for GBM treatment. In this review, we discussed the unique features of TAMs in GBMs, including their origin, the tumor-supportive properties, the secreted cytokines, and the relevant mechanisms. In addition, we tried to interpret the current understandings about the interplay between GBM cancer cells and TAMs. Finally, the translational studies of targeting TAMs were also described.

  17. Larynx carcinoma regulates tumor-associated macrophages through PLGF signaling.

    Science.gov (United States)

    Zhou, Xu; Qi, Ying

    2015-01-01

    Cancer neovascularization plays an essential role in the metastasis of larynx carcinoma (LC). However, the underlying molecular mechanisms are not completely understood. Recently, we reported that placental growth factor (PLGF) regulates expression of matrix metalloproteinase 3 (MMP3) through ERK/MAPK signaling pathway in LC. Here, we show that MMP9 upregulated in LC, and appeared to be mainly produced by M2 macrophages (tumor-associated macrophages (TAM)). In a transwell co-culture system, PLGF secreted by LC cells triggered macrophage polarization to a TAM subtype that releases MMP9. Moreover, MMP9 was found to be activated in the PLGF-polarized TAM via transforming growth factor β (TGFβ) receptor signaling activation. Furthermore, PLGF in LC cells induced macrophage polarization in vivo, and significantly promoted the growth of LC. Thus, together with our previous work, our study highlights a pivotal role of cross-talk between TAM and LC in regulating the metastasis of LC. PMID:25961789

  18. 一种新型免疫传感器阵列检测癌胚抗原和糖类抗原199技术%A New Type of Sensor Array Detection of Carcinoembryonic Antigen and Carbohydrate Antigen 199 Technology

    Institute of Scientific and Technical Information of China (English)

    周靖; 胡富陶; 余红卫

    2015-01-01

    制备了一种新型的含2个包覆分子印迹聚合物的丝网印刷碳工作电极的电化学发光夹心免疫传感器阵列,通过该阵列实现了肿瘤标志物癌胚抗原(CEA)和糖类抗原199(CA199)的近同时免疫分析。该新型的电化学发光免疫方法将空间分辨技术与分子印迹技术相结合,为 CEA 和CA199的复合免疫分析提供了一条简单、低成本、快速和灵敏的途径。该方法对临床实验中多种蛋白质的近同时测定也显示了较大的潜力。%In this study, a novel electrochemiluminescence (ECL) immunosensor array is engineered consisting of two screen-printed carbon working electrodes coated with molecular imprinting polymer (MIPs). The array is formed to perform multiplexed immunoassay of tumor markers (carcinoembryonic antigen (CEA) and carbohydrate antigen-199 (CA199)). Based on spatial-resolved technique, and coupled with molecularly imprinted technique, this novel ECL strategy provides a simple, low-cost, fast and sensitive approach for multiplexed immunoassay of CEA and CA199. This approach may render promising potential for protein detection in the circumstances of clinical laboratory setting.

  19. Enhanced interferon-γ secretion and antitumor activity of T-lymphocytes activated by dendritic cells loaded with glycoengineered myeloma antigens

    Institute of Scientific and Technical Information of China (English)

    XIONG Hong; WU Qiu-ye; HU Hong-gang; LIU Ban; GUO Zhong-wu; Daniel Man-yuan Sze; HOU Jian

    2007-01-01

    Background Immunotherapy is emerging as a promising cure for cancer. However, a severe problem in this area is the immune tolerance to tumor cells and tumor-associated antigens, as evidenced by the ability of cancer to escape immune surveillance. To overcome this problem this work examined the potential of improving the antigenicity of myeloma by metabolic engineering of its cell surface carbohydrate antigens (i.e., glycoengineering) and presentation of the modified tumor antigens by dendritic cells (DCs) to generate cytotoxic T-lymphocytes (CTLs).Methods CD138+ myeloma cells were isolated from 11 multipe myeloma (MM) patients by the immunomagnetic bead method. The MM cells were treated with N-propionyl-D-mannosamine (ManNPr), a synthetic analog of N-acetyl-D-mannosamine (ManNAc), the natural biosynthetic precursor of N-acetyl sialic acid (NeuNAc), to express unnatural N-propionylated sialoglycans. The giycoengineered cells were then induced to apoptosis, and the apoptotic products were added to cultured functional DCs that could present the unnatural carbohydrate antigens to autologous T-lymphocytes.Results It was found that the resultant DCs could activate CD4+ and CD8+ T-lymphocytes, resulting in increased expression of T cell surface markers, including CD8CD28 and CD4CD29. Moreover, upon stimulation by glycoengineered MM cells, these DC-activated T-lymphocytes could release significantly higher levels of IFN-γ (P<0.05).Lactate dehydrogenase (LDH) assays further showed that the stimulated T-lymphocytes were cytotoxic to glycoengineered MM cells.Conclusions This work demonstrated that glycoengineered myeloma cells were highly antigenic and the CTLs induced by the DCs loaded with the unnatural myeloma antigens were specifically cytotoxic to the glycoengineered myeloma.This may provide a new strategy for overcoming the problem of immune tolerance for the development of effective immunotherapies for MM.

  20. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    Energy Technology Data Exchange (ETDEWEB)

    Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Khan, Gazala [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2013-05-01

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  1. Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

    International Nuclear Information System (INIS)

    Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

  2. Protein L: a novel reagent for the detection of Chimeric Antigen Receptor (CAR) expression by flow cytometry

    OpenAIRE

    Zheng Zhili; Chinnasamy Nachimuthu; Morgan Richard A

    2012-01-01

    Abstract Background There has been significant progress in the last two decades on the design of chimeric antigen receptors (CAR) for adoptive immunotherapy targeting tumor-associated antigens. Structurally CARs consist of a single chain antibody fragment directed against a tumor-associated antigen fused to an extracellular spacer and transmembrane domain followed by T cell cytoplasmic signaling moieties. Currently several clinical trials are underway using gene modified peripheral blood lymp...

  3. Tumor Expression of the Carcinoembryonic Antigen Correlates with High Mitotic Activity and Cell Pleomorphism Index in Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    Rancés Blanco

    2013-01-01

    Full Text Available At present, some research efforts are focusing on the evaluation of a variety of tumor associated antigens (TAAs for a better understanding of tumor biology and genetics of lung tumors. For this reason, we evaluated the tissue expression of carcinoembryonic antigen (CEA and ior C2 (a cell surface O-linked glycoprotein carbohydrate chain TAA in lung carcinomas, as well as its correlation with a variety of clinicopathological features. The tissue expression of CEA was evidenced in 22/43 (51.16% lung carcinomas and it was correlated with mitotic activity, cell pleomorphism indexes, and age of patients. The expression of ior C2 was observed in 15/43 (34.88% tumors but no correlation with the clinicopathological features mentioned above was obtained. No correlation between both CEA and ior C2 antigens expression and the overall survival (OS of non-small-cell lung cancer patients was also observed. However, CEA-negative patients displayed higher OS rates as compared with positive ones (69.74 versus 58.26 months. Our results seem to be in agreement with the role of CEA expression in tumor cell proliferation, inhibition of cell polarizations and tissue architecture distortion. The significance of ior C2 antigen in these malignancies and it potential use in diagnosis, prognosis, and/or immunotherapy must be reevaluated.

  4. Isolation of Mouse and Human Tumor-Associated Macrophages.

    Science.gov (United States)

    Cassetta, Luca; Noy, Roy; Swierczak, Agnieszka; Sugano, Gaël; Smith, Harriet; Wiechmann, Lisa; Pollard, Jeffrey W

    2016-01-01

    The tumor microenvironment is a complex network of cells that support tumor progression and malignancy. It has been demonstrated that tumor cells can educate the immune system to promote a tumor-friendly environment. Among all these immune cells, tumor-associated macrophages (TAMs) are well represented and their presence in mouse models has been shown to promote tumor progression and metastasis. These effects are through the stimulation of angiogenesis, enhancement of tumor cell invasion and intravasation, immunosuppression, and at the metastatic site tumor cell extravasation and growth. However, the precise mechanisms are not fully understood. Furthermore there is limited information on TAMs derived from human cancers. For this reason it is important to be able to extract TAMs from tumors in order to compare their phenotypes, functions, and transcriptomes with normal resident tissue macrophages. Isolation of these cells is challenging due to the lack of markers and standardized protocols. Here we show an optimized protocol for the efficient isolation and extraction of resident macrophages and TAMs from human and mouse tissues by using multicolor flow cytometry. These protocols allow for the extraction of thousands of macrophages in less than 5 h from tissues as small as half a gram. The isolated macrophages can then be used for both "omics" and in vitro studies. PMID:27325269

  5. Genome wide in silico SNP-tumor association analysis

    International Nuclear Information System (INIS)

    Carcinogenesis occurs, at least in part, due to the accumulation of mutations in critical genes that control the mechanisms of cell proliferation, differentiation and death. Publicly accessible databases contain millions of expressed sequence tag (EST) and single nucleotide polymorphism (SNP) records, which have the potential to assist in the identification of SNPs overrepresented in tumor tissue. An in silico SNP-tumor association study was performed utilizing tissue library and SNP information available in NCBI's dbEST (release 092002) and dbSNP (build 106). A total of 4865 SNPs were identified which were present at higher allele frequencies in tumor compared to normal tissues. A subset of 327 (6.7%) SNPs induce amino acid changes to the protein coding sequences. This approach identified several SNPs which have been previously associated with carcinogenesis, as well as a number of SNPs that now warrant further investigation This novel in silico approach can assist in prioritization of genes and SNPs in the effort to elucidate the genetic mechanisms underlying the development of cancer

  6. Nectin-4 is a new histological and serological tumor associated marker for breast cancer

    Directory of Open Access Journals (Sweden)

    Sauvan Richard

    2007-05-01

    correlate with the number of metastases (P = 0.038. Serum Nectin-4 is also a marker of therapeutic efficiency and correlates, in 90% of cases, with clinical evolution. Conclusion Nectin-4 is a new tumor-associated antigen for breast carcinoma. Nectin-4 is a new bio-marker whose use could help refine breast cancer taxonomy and improve patients' follow-up. Nectin-4 emerges as a potential target for breast cancer immunotherapy.

  7. Further characterization of filarial antigens by SDS polyacrylamide gel electrophoresis

    OpenAIRE

    Dissanayake, S.; Galahitiyawa, S. C.; Ismail, M. M.

    1983-01-01

    SDS (sodium dodecyl sulfate)-polyacrylamide gel electrophoresis of an antigen isolated from sera of Wuchereria bancrofti-infected patients and Setaria digitata antigen SD2-4 is reported. Both antigens showed carbohydrate (glycoprotein) staining. The W. bancrofti antigen had an apparent relative molecular mass of 35 000 while the S. digitata antigen SD2-4 migrated at the marker dye position on SDS-polyacrylamide gel electrophoresis. SDS treatment of these antigens did not abolish the precipita...

  8. Dexamethasone alleviates tumor-associated brain damage and angiogenesis.

    Directory of Open Access Journals (Sweden)

    Zheng Fan

    Full Text Available Children and adults with the most aggressive form of brain cancer, malignant gliomas or glioblastoma, often develop cerebral edema as a life-threatening complication. This complication is routinely treated with dexamethasone (DEXA, a steroidal anti-inflammatory drug with pleiotropic action profile. Here we show that dexamethasone reduces murine and rodent glioma tumor growth in a concentration-dependent manner. Low concentrations of DEXA are already capable of inhibiting glioma cell proliferation and at higher levels induce cell death. Further, the expression of the glutamate antiporter xCT (system Xc-; SLC7a11 and VEGFA is up-regulated after DEXA treatment indicating early cellular stress responses. However, in human gliomas DEXA exerts differential cytotoxic effects, with some human glioma cells (U251, T98G resistant to DEXA, a finding corroborated by clinical data of dexamethasone non-responders. Moreover, DEXA-resistant gliomas did not show any xCT alterations, indicating that these gene expressions are associated with DEXA-induced cellular stress. Hence, siRNA-mediated xCT knockdown in glioma cells increased the susceptibility to DEXA. Interestingly, cell viability of primary human astrocytes and primary rodent neurons is not affected by DEXA. We further tested the pharmacological effects of DEXA on brain tissue and showed that DEXA reduces tumor-induced disturbances of the microenvironment such as neuronal cell death and tumor-induced angiogenesis. In conclusion, we demonstrate that DEXA inhibits glioma cell growth in a concentration and species-dependent manner. Further, DEXA executes neuroprotective effects in brains and reduces tumor-induced angiogenesis. Thus, our investigations reveal that DEXA acts pleiotropically and impacts tumor growth, tumor vasculature and tumor-associated brain damage.

  9. Regulatory T Cells in Tumor-Associated Tertiary Lymphoid Structures Suppress Anti-tumor T Cell Responses.

    Science.gov (United States)

    Joshi, Nikhil S; Akama-Garren, Elliot H; Lu, Yisi; Lee, Da-Yae; Chang, Gregory P; Li, Amy; DuPage, Michel; Tammela, Tuomas; Kerper, Natanya R; Farago, Anna F; Robbins, Rebecca; Crowley, Denise M; Bronson, Roderick T; Jacks, Tyler

    2015-09-15

    Infiltration of regulatory T (Treg) cells into many tumor types correlates with poor patient prognoses. However, mechanisms of intratumoral Treg cell function remain to be elucidated. We investigated Treg cell function in a genetically engineered mouse model of lung adenocarcinoma and found that Treg cells suppressed anti-tumor responses in tumor-associated tertiary lymphoid structures (TA-TLSs). TA-TLSs have been described in human lung cancers, but their function remains to be determined. TLSs in this model were spatially associated with >90% of tumors and facilitated interactions between T cells and tumor-antigen-presenting dendritic cells (DCs). Costimulatory ligand expression by DCs and T cell proliferation rates increased in TA-TLSs upon Treg cell depletion, leading to tumor destruction. Thus, we propose that Treg cells in TA-TLSs can inhibit endogenous immune responses against tumors, and targeting these cells might provide therapeutic benefit for cancer patients.

  10. Clinical significant of combined determination of serum CEA and carbohydrate antigen tumor markers in 85 patients with lung adenocarcinoma%肺腺癌患者血清CEA和糖链抗原肿瘤标记物联合测定的临床意义

    Institute of Scientific and Technical Information of China (English)

    沈粉秧

    2014-01-01

    Objective To explore the clinical significant of combined determination of serum CEA and car-bohydrate antigen (CA125, CA199, CA153) tumor markers in patients with lung adenocarcinoma. Methods The serum CEA and carbohydrate antigen (CA125, CA199 and CA153) levels were determined with chemilumescence immunoassay in 85 patients with lung adenocarcinoma, 35 patients with lung squanous carcinoma, 42 patients with small cell lung cancer and 49 patients with benign lung disease. Results In 162 patients with lung cancer, the ser-um CEA and carbohydrate antigen levels were significantly higher in 85 patients with lung adenocarcinoma, 35 pa-tients with lung squanous carcinoma and 42 patients with small cell lung cancer than those in 49 patients with benign lung disease (P<0. 001) and the level of 85 patients with lung adenocarcinoma was the highest. So did the serum carbohydrate antigen levels. The sensitivity (95. 29%) and accuracy (83. 76%) in the four tumor markers combined determination were significantly higher than those in single item ( P all<0. 01 ) , and the specificity was 75. 23%. Conclusion The combined detection of serum CEA and carbohydrate antigen levels is helpful for the diagnosis of lung adenocarcinoma, with higher sensitivity and accuracy.%目的:为了探讨85例肺腺癌患者血清CEA和糖链抗原肿瘤标记物水平联合测定的临床意义。方法化学发光免疫分析测定85例肺腺癌、35例肺鳞癌、42例小细胞肺癌和49例良性肺部疾病血清CEA和糖链抗原(CA125、CA199和CA153)水平,并进行了比较性研究。结果162例肺癌患者中,85例肺腺癌、35例肺鳞癌、42例小细胞肺癌患者血清CEA水平较之49例良性肺部疾病明显增高( P<0.001、P<0.01和P<0.001),以肺腺癌增高最为明显。血清糖链抗原(CA125、CA199和 CA153)水平亦然,也以肺腺癌血清CA125、CA199和CA153水平增高最为显著。四项肿瘤标记物的联合测定对85例肺腺癌的敏感性为95.29

  11. Tissue distribution of histo-blood group antigens

    DEFF Research Database (Denmark)

    Ravn, V; Dabelsteen, Erik

    2000-01-01

    The introduction of immunohistochemical techniques and monoclonal antibodies to specific carbohydrate epitopes has made it possible to study in detail the tissue distribution of histo-blood group antigens and related carbohydrate structures. The present paper summarizes the available data...... concerning the histological distribution of histo-blood group antigens and their precursor structures in normal human tissues. Studies performed have concentrated on carbohydrate antigens related to the ABO, Lewis, and TTn blood group systems, i.e. histo-blood group antigens carried by type 1, 2, and 3 chain...... carrier carbohydrate chains. Histo-blood group antigens are found in most epithelial tissues. Meanwhile, several factors influence the type, the amount, and the histological distribution of histoblood group antigens, i.e. the ABO, Lewis, and saliva-secretor type of the individual, and the cell- and tissue...

  12. Carbohydrate Metabolism Disorders

    Science.gov (United States)

    ... you eat. Food is made up of proteins, carbohydrates, and fats. Chemicals in your digestive system (enzymes) ... metabolic disorder, something goes wrong with this process. Carbohydrate metabolism disorders are a group of metabolic disorders. ...

  13. The antigen specific composition of melanoma tumor infiltrating lymphocytes?

    DEFF Research Database (Denmark)

    Hadrup, Sine Reker

    2012-01-01

    Large numbers of tumor associated antigens has been characterized, but only a minor fraction of these are recognized by tumor infiltrating lymphocytes of melanoma, although these have shown the ability to recognize tumor and provide tumor regression upon adoptive transfer. Thus the peptide...... recognition of the majority of the CD8 tumor infiltrating lymphocytes remains to be identified....

  14. Carbohydrates in Supramolecular Chemistry.

    Science.gov (United States)

    Delbianco, Martina; Bharate, Priya; Varela-Aramburu, Silvia; Seeberger, Peter H

    2016-02-24

    Carbohydrates are involved in a variety of biological processes. The ability of sugars to form a large number of hydrogen bonds has made them important components for supramolecular chemistry. We discuss recent advances in the use of carbohydrates in supramolecular chemistry and reveal that carbohydrates are useful building blocks for the stabilization of complex architectures. Systems are presented according to the scaffold that supports the glyco-conjugate: organic macrocycles, dendrimers, nanomaterials, and polymers are considered. Glyco-conjugates can form host-guest complexes, and can self-assemble by using carbohydrate-carbohydrate interactions and other weak interactions such as π-π interactions. Finally, complex supramolecular architectures based on carbohydrate-protein interactions are discussed. PMID:26702928

  15. The serum carbohydrate antigen 125 and carcinoembryonic antigen comparsion for the han and uyghur patients of terminal gallbladder cancer in xinjiang uygur autonomous region%新疆地区汉族与维吾尔族晚期胆囊癌患者血清糖类抗原125、癌胚抗原水平比较

    Institute of Scientific and Technical Information of China (English)

    毛拉艾沙·买买提; 薛峰; 依马木买买提江·阿不拉

    2013-01-01

    目的 比较新疆地区汉族与维吾尔族晚期胆囊癌患者血清糖类抗原125(CA125)、癌胚抗原(CEA)水平是否存在差异.方法 原发性晚期胆囊癌患者80例,其中维吾尔族40例,汉族40例;随机选取同期住院的胆囊炎患者60例作为对照组,其中维吾尔族34例,汉族26例;均进行血清CA125、CEA检测.结果 胆囊癌组的汉族、维吾尔族患者与对照组同民族患者CA125、CEA水平差异均有统计学意义(t=27.01、28.06、10.68、11.25,均P<0.05);而两组内汉族、维吾尔族患者间的CA125、CEA水平差异均无统计学意义(t=0.47、0.34、0.11、1.23,均P>0.05);胆囊癌Ⅳ期汉族、维吾尔族患者与Ⅴ期同民族患者CA125、CEA水平差异均有统计学意义(t=26.92、25.01、16.58、14.54,均P<0.05);汉族、维吾尔族的胆囊癌Ⅳ期患者之间、Ⅴ期患者之间的CA125、CEA水平差异均无统计学意义(t=1.13、0.11、0.38、0.07,均P>0.05).结论 新疆地区汉族与维吾尔族晚期胆囊癌患者血清CA125、CEA水平无差异,晚期胆囊癌患者进行CA125、CEA检测有助于病情诊断.%Objective To compare the differences on the serum carbohydrate antigen 125 and carcinoembryonic antigen for the Han and Uyghur patients of terminal gallbladder cancer in Xinjiang Uygur Autonomous Region.Methods 80 cases of patients with primary advanced gallbladder,including 40 cases of Uighur,Han 40 cases,The cholecystitis patients randomly selected from the same period of hospitalization of 60 cases as the control group.Including 34 cases of Uighur and Han 26 cases,Levels of serum CA125,CEA were detected.Results The gallbladder group of Han,Uygur patients and the control group with ethnic patients CA125,CEA level differences were statistically significant(t =27.01,28.06,10.68,11.25,all P < 0.05) ; CA125,CEA level differences between the two groups within the Han,Uygur patients were not statistically significant(t =0.47,0.34,0.1 l,1.23,all P > 0

  16. Radioiodinated branched carbohydrates

    Science.gov (United States)

    Goodman, Mark M.; Knapp, Jr., Furn F.

    1989-01-01

    A radioiodinated branched carbohydrate for tissue imaging. Iodine-123 is stabilized in the compound by attaching it to a vinyl functional group that is on the carbohydrate. The compound exhibits good uptake and retention and is promising in the development of radiopharmaceuticals for brain, heart and tumor imaging.

  17. Cell surface carbohydrate changes during embryonic and fetal skin development

    DEFF Research Database (Denmark)

    Dabelsteen, Erik; Holbrook, K; Clausen, H;

    1986-01-01

    Monoclonal antibodies to four type 2 chain carbohydrate antigens were used for immunohistochemical studies of embryonic and fetal skin. The antibodies detected N-acetyllactosamine and 3 fucosyl substitutes of this, blood group antigen H, Lex, and Ley. Periderm consistently stained for N-acetyllac......Monoclonal antibodies to four type 2 chain carbohydrate antigens were used for immunohistochemical studies of embryonic and fetal skin. The antibodies detected N-acetyllactosamine and 3 fucosyl substitutes of this, blood group antigen H, Lex, and Ley. Periderm consistently stained for N...... maximally expressed at the early stages of development, but may later be modified either by sialylation or fucosylation into blood group H or Lex, or by Ley substances, respectively. The orderly and well-defined changes observed during skin differentiation are in agreement with other studies, which have...

  18. Computerized molecular modeling of carbohydrates

    Science.gov (United States)

    Computerized molecular modleing continues to increase in capability and applicability to carbohydrates. This chapter covers nomenclature and conformational aspects of carbohydrates, perhaps of greater use to carbohydrate-inexperienced computational chemists. Its comments on various methods and studi...

  19. Tumor-associated fibroblasts as "Trojan Horse" mediators of resistance to anti-VEGF therapy.

    Science.gov (United States)

    Francia, Giulio; Emmenegger, Urban; Kerbel, Robert S

    2009-01-01

    While targeting VEGF has shown success against a number of human cancers, drug resistance has resulted in compromised clinical benefits. In this issue of Cancer Cell, Crawford et al. (2009) report that tumors resistant to anti-VEGF therapy stimulate tumor-associated fibroblasts to express proangiogenic PDGF-C, implicating it as a potential therapeutic target.

  20. An Ultrasensitive Electrochemiluminescence Immunoassay for Carbohydrate Antigen 19-9 in Serum Based on Antibody Labeled Fe3O4 Nanoparticles as Capture Probes and Graphene/CdTe Quantum Dot Bionanoconjugates as Signal Amplifiers

    Science.gov (United States)

    Gan, Ning; Zhou, Jing; Xiong, Ping; Li, Tianhua; Jiang, Shan; Cao, Yuting; Jiang, Qianli

    2013-01-01

    The CdTe quantum dots (QDs), graphene nanocomposite (CdTe-G) and dextran–Fe3O4 magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL) immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9) in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe3O4) for enriching CA 19-9 were synthesized by immobilizing the CA 19-9’s first antibody (CA 19-9 Ab1) on magnetic nanoparticles (dextran-Fe3O4). Secondly, the signal probes (CA 19-9 Ab2/CdTe-G), which can emit an ECL signal, were formed by attaching the secondary CA 19-9 antibody (CA 19-9 Ab2) to the surface of the CdTe-G. Thirdly, the above two probes were used for conjugating with a serial of CA 19-9 concentrations. Graphene can immobilize dozens of CdTe QDs on their surface, which can emit stronger ECL intensity than CdTe QDs. Based on the amplified signal, ultrasensitive antigen detection can be realized. Under the optimal conditions, the ECL signal depended linearly on the logarithm of CA 19-9 concentration from 0.005 to 100 pg/mL, and the detection limit was 0.002 pg/mL. Finally, five samples of human serum were tested, and the results were compared with a time-resolved fluorescence assay (TRFA). The novel immunoassay provides a stable, specific and highly sensitive immunoassay protocol for tumor marker detection at very low levels, which can be applied in early diagnosis of tumor. PMID:23685872

  1. An Ultrasensitive Electrochemiluminescence Immunoassay for Carbohydrate Antigen 19-9 in Serum Based on Antibody Labeled Fe3O4 Nanoparticles as Capture Probes and Graphene/CdTe Quantum Dot Bionanoconjugates as Signal Amplifiers

    Directory of Open Access Journals (Sweden)

    Ning Gan

    2013-05-01

    Full Text Available The CdTe quantum dots (QDs, graphene nanocomposite (CdTe-G and dextran–Fe3O4 magnetic nanoparticles have been synthesized for developing an ultrasensitive electrochemiluminescence (ECL immunoassay for Carcinoembryonic antigen 19-9 (CA 19-9 in serums. Firstly, the capture probes (CA 19-9 Ab1/Fe3O4 for enriching CA 19-9 were synthesized by immobilizing the CA 19-9’s first antibody (CA 19-9 Ab1 on magnetic nanoparticles (dextran-Fe3O4. Secondly, the signal probes (CA 19-9 Ab2/CdTe-G, which can emit an ECL signal, were formed by attaching the secondary CA 19-9 antibody (CA 19-9 Ab2 to the surface of the CdTe-G. Thirdly, the above two probes were used for conjugating with a serial of CA 19-9 concentrations. Graphene can immobilize dozens of CdTe QDs on their surface, which can emit stronger ECL intensity than CdTe QDs. Based on the amplified signal, ultrasensitive antigen detection can be realized. Under the optimal conditions, the ECL signal depended linearly on the logarithm of CA 19-9 concentration from 0.005 to 100 pg/mL, and the detection limit was 0.002 pg/mL. Finally, five samples of human serum were tested, and the results were compared with a time-resolved fluorescence assay (TRFA. The novel immunoassay provides a stable, specific and highly sensitive immunoassay protocol for tumor marker detection at very low levels, which can be applied in early diagnosis of tumor.

  2. Perspectives and limits of an immunoenzymatic assay (ELISA) for herpes simplex virus (HSV) tumor-associated antigen (TAA).

    Science.gov (United States)

    Tarro, G; D'Alessandro, G; Esposito, C; Flaminio, G; Mascolo, A; Maturo, S

    1981-01-01

    An ELISA has been developed to detect specific antibodies for HSV-TAA in sera of patients with head, neck and urogenital tract carcinomas (Cancer, 45:1980). Further studies have shown that 64/800 controls (8.12%), i.e. healthy people, are positive against 312/425 patients with herpes associated tumors (73.41%). People with herpes recurrens show 18% positivity, precancerous lesions 44% and other cancers 6%. Immunodepression, chemo- and radio-therapy play an inhibitory role on the ELISA positivity for TAA. Radical surgery of the HSV-TAA positive cancers results in lack of specific antibody whereas relapse or metastasis of the tumor yields positive results. The reproducibility of the test is very good and the standard error is low (1.0655). The conclusions allow us to foresee the use of this ELISA for early detection of the HSV-TAA antibodies in certain human carcinomas.

  3. Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases.

    Science.gov (United States)

    Zhong, Gen-Shen; Wu, Min-Na; Guo, Xiao-Fang; Zhang, Sheng-Hua; Miao, Qing-Fang; Zhen, Yong-Su

    2012-10-01

    Gelatinases play an important role in tumor growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumors. Lidamycin is an enediyne antitumor antibiotic with potent cytotoxicity. We previously reported that a tandem scFv format (dFv-LDP-AE) showed enhanced binding ability with gelatinases compared with the scFv-lidamycin conjugate (Fv-LDP-AE). In this study, the antitumor activities of dFv-LDP-AE on hepatocellular carcinoma (HCC) were evaluated in vitro and in vivo. By SDS-PAGE analysis, it was found that partial fusion protein dFv-LDP existed as dimer; the results of ELISA and immunofluorescence demonstrated that the fusion protein dFv-LDP could efficiently bind to hepatoma cells in vitro. The apparent arrest of cell cycle at G2/M phase and induction of apoptosis at nanomole levels indicated that the dFv-LDP-AE was very potent against HCC. In in vivo experiments, dFv-LDP-AE shown enhanced cytotoxic effects compared to those of LDM. Administration at mouse tolerable dosage level, the inhibition rate of tumor growth was 89.5% of dFv-LDP-AE vs. 73.6% of LDM on transplantable H22 in mice (Penediyne-energized fusion protein dFv-LDP-AE showed potential application as a new agent for therapeutic appications in HCC. PMID:22797730

  4. Structural and Functional Studies of Peptide-Carbohydrate Mimicry

    Science.gov (United States)

    Johnson, Margaret A.; Pinto, B. Mario

    Certain peptides act as molecular mimics of carbohydrates in that they are specifically recognized by carbohydrate-binding proteins. Peptides that bind to anti-carbohydrate antibodies, carbohydrate-processing enzymes, and lectins have been identified. These peptides are potentially useful as vaccines and therapeutics; for example, immunologically functional peptide molecular mimics (mimotopes) can strengthen or modify immune responses induced by carbohydrate antigens. However, peptides that bind specifically to carbohydrate-binding proteins may not necessarily show the corresponding biological activity, and further selection based on biochemical studies is always required. The degree of structural mimicry required to generate the desired biological activity is therefore an interesting question. This review will discuss recent structural studies of peptide-carbohydrate mimicry employing NMR spectroscopy, X-ray crystallography, and molecular modeling, as well as relevant biochemical data. These studies provide insights into the basis of mimicry at the molecular level. Comparisons with other carbohydrate-mimetic compounds, namely proteins and glycopeptides, will be drawn. Finally, implications for the design of new therapeutic compounds will also be presented.

  5. Carbohydrates and Depression.

    Science.gov (United States)

    Wurtman, Richard J.; Wurtman, Judith J.

    1989-01-01

    Describes the symptoms, such as appetite change and mood fluctuation, basic mechanisms, and some treatments of Seasonal Affective Disorder (SAD), Carbohydrate-Craving Obesity (CCO) and Premenstrual Syndrome (PMS). Provides several tables and diagrams, and three reading references. (YP)

  6. Monoclonal antibody-defined human pancreatic cancer-associated antigens.

    Science.gov (United States)

    Schmiegel, W H; Kalthoff, H; Arndt, R; Gieseking, J; Greten, H; Klöppel, G; Kreiker, C; Ladak, A; Lampe, V; Ulrich, S

    1985-03-01

    Three pancreatic cancer-associated antigens were characterized by use of monoclonal antibodies in immunobinding studies with various cellular and soluble target antigens, in immunoprecipitation, and in immunoperoxidase staining. C54-0 represents a tumor-associated Mr 122,000 antigen, which appears to be widely distributed on various epithelial tumors and to a lower extent on normal tissue. C1-N3 antigen exhibited a more restricted distribution, reacting with pancreatic and various gastrointestinal tract tumors as well as with chronically inflamed pancreatic tissue. The most specific antigen expression was observed for C1-P83 antigen, found on all exocrine tumors of the pancreas, but not on normal or chronically inflamed pancreatic tissue.

  7. Telomere profiles and tumor-associated macrophages with different immune signatures affect prognosis in glioblastoma.

    Science.gov (United States)

    Hung, Noelyn A; Eiholzer, Ramona A; Kirs, Stenar; Zhou, Jean; Ward-Hartstonge, Kirsten; Wiles, Anna K; Frampton, Chris M; Taha, Ahmad; Royds, Janice A; Slatter, Tania L

    2016-03-01

    Telomere maintenance is a hallmark of cancer and likely to be targeted in future treatments. In glioblastoma established methods of identifying telomerase and alternative lengthening of telomeres leave a significant proportion of tumors with no defined telomere maintenance mechanism. This study investigated the composition of these tumors using RNA-Seq. Glioblastomas with an indeterminate telomere maintenance mechanism had an increased immune signature compared with alternative lengthening of telomeres and telomerase-positive tumors. Immunohistochemistry for CD163 confirmed that the majority (80%) of tumors with an indeterminate telomere maintenance mechanism had a high presence of tumor-associated macrophages. The RNA-Seq and immunostaining data separated tumors with no defined telomere maintenance mechanism into three subgroups: alternative lengthening of telomeres like tumors with a high presence of tumor-associated macrophages and telomerase like tumors with a high presence of tumor-associated macrophages. The third subgroup had no increase in tumor-associated macrophages and may represent a distinct category. The presence of tumor-associated macrophages conferred a worse prognosis with reduced patient survival times (alternative lengthening of telomeres with and without macrophages P=0.0004, and telomerase with and without macrophages P=0.013). The immune signatures obtained from RNA-Seq were significantly different between telomere maintenance mechanisms. Alternative lengthening of telomeres like tumors with macrophages had increased expression of interferon-induced proteins with tetratricopeptide repeats (IFIT1-3). Telomerase-positive tumors with macrophages had increased expression of macrophage receptor with collagenous structure (MARCO), CXCL12 and sushi-repeat containing protein x-linked 2 (SRPX2). Telomerase-positive tumors with macrophages were also associated with a reduced frequency of total/near total resections (44% vs >76% for all other subtypes

  8. Mushroom β-Glucan May Immunomodulate the Tumor-Associated Macrophages in the Lewis Lung Carcinoma

    Directory of Open Access Journals (Sweden)

    Wan-Jhen Wang

    2015-01-01

    Full Text Available The present study showed that oral mushroom beta-glucan treatment significantly increased IFN-γ mRNA expression but significantly reduced COX-2 mRNA expression within the lung. For LLC tumor model, oral Ganoderma lucidum or Antrodia camphorata polysaccharides treatments significantly reduced TGF-β production in serum. In addition, IL-12 and IFN-γ mRNA expression were significantly increased, but IL-6, IL-10, COX-2, and TGF-β mRNA expression were substantially following oral mushroom polysaccharides treatments. The study highlights the efficacious effect of mushroom polysaccharides for ameliorating the immune suppression in the tumor microenvironment. Increased M1 phenotype of tumor-associated macrophages and attenuated M2 phenotype of tumor-associated macrophages could be achieved by ingesting mushroom polysaccharides.

  9. Comparative activation states of tumor-associated and peritoneal macrophages from mice bearing an induced fibrosarcoma.

    Science.gov (United States)

    Valdez, J C; de Alderete, N; Meson, O E; Sirena, A; Perdigon, G

    1990-11-01

    Balb/c mice bearing a methylcholanthrene-induced fibrosarcoma were used to compare the activation levels of tumor-associated and peritoneal macrophages. Two stages of tumor growth were examined, namely "small" and "large" tumors, with average diameters of 10 and 30 mm, respectively. The activation state, determined by measurement of both phagocytic index and beta-glucuronidase content, was found to be markedly higher in tumor-associated macrophages than in their peritoneal counterparts and it was, in addition, independent of tumor progression. The percentage of tumor-associated macrophages, which were detected on the basis of Fc receptor expression, remained constant in the growing neoplasm, at approximately 23% of total cell population. None of these parameters were affected by inoculation with an immunopotentiating dose of heat-killed Candida albicans which, on the other hand, seemed not to alter the course of the tumor. These data suggest that within the tumor microenvironment macrophages would somehow be maintained at a constant proportion and at a highly activated state, while outside the tumor they would be at a lower activation level. Our results also suggest that TAM would not possess antitumor activity in vivo, although we have found this activity in vitro.

  10. Leishmania braziliensis: isolation of carbohydrate-containing antigen and possibility of its use in the immunodiagnosis of American Cutaneous Leishmaniasis Leishmania braziliensis: isolamento de antígeno contendo carboidrato e a possibilidade de sua aplicação no imunodiagnóstico da Leishmaniose Tegumentar Americana

    Directory of Open Access Journals (Sweden)

    T. G. V. Silveira

    1995-06-01

    Full Text Available Leishmania braziliensis is a causative agent of American Cutaneous Leishmaniasis (ACL. The 034-JCG strain, isolated from a patient from the northern region of Paraná State, Brazil, was cultivated in Blood Agar Base medium, lyophilized and submitted to phenol-water extraction. The extract was treated with RNase I. The carbohydrate containing-antigen (Ag-CHO was immunogenic to rabbits and showed at least a fraction with some negative charge at pH 8.2. This antigen showed cross-reactivity with the phenol-water extract of the growth medium used for the culture of promastigotes and with the surface antigens of promastigotes. Its composition is: 24.3% of total sugars, from which 11.2% of galactose, 7.5% of mannose and 5.6% of ribose. Protein content was 5.4% and phosphate 18.5%. The antigenic activity was maintained after: repeated freezing-thawing; lyophilization; heating at 100ºC for 30 minutes; treatment with RNase, trichloroacetic acid and sodium metaperiodate. The precipitin line obtained is Periodic Acid Schiff positive. The application of the Ag-CHO in counterimmunoelectrophoresis reaction for the immunodiagnosis of ACL showed 60% sensitivity, and no cross-reaction with the five sera of Chagas' disease patients tested. The use of this antigen in a more sensitive technique, with more samples of sera, may improve these results.A Leishmania braziliensis é um dos agentes causadores da Leishmaniose Tegumentar Americana (LTA. A cepa 034-JCG, isolada de paciente da região norte do estado do Paraná, Brasil, foi cultivada em meio Blood Agar Base, liofilizada e submetida a extração com fenol-água e o extrato obtido foi tratado com RNase I. O antígeno contendo carboidrato (Ag-CHO mostrou-se imunogênico para coelhos e apresentou pelo menos uma fração com poucas cargas negativas em pH 8,2. Este antígeno apresenta reação cruzada com extrato fenólico do meio de cultura usado para o cultivo de promastigotas e com antígenos de superfície de

  11. Complex carbohydrates (image)

    Science.gov (United States)

    ... foods such as peas, beans, whole grains, and vegetables. Both simple and complex carbohydrates are turned to glucose (blood sugar) in the body and are used as energy. Glucose is used in the cells of the body and in the brain. Any ...

  12. Inflamed tumor-associated adipose tissue is a depot for macrophages that stimulate tumor growth and angiogenesis

    NARCIS (Netherlands)

    Wagner, Marek; Bjerkvig, Rolf; Wiig, Helge; Melero-Martin, Juan M.; Lin, Ruei-Zeng; Klagsbrun, Michael; Dudley, Andrew C.

    2012-01-01

    Tumor-associated stroma is typified by a persistent, non-resolving inflammatory response that enhances tumor angiogenesis, growth and metastasis. Inflammation in tumors is instigated by heterotypic interactions between malignant tumor cells, vascular endothelium, fibroblasts, immune and inflammatory

  13. Carbohydrates and dietary fiber.

    Science.gov (United States)

    Suter, P M

    2005-01-01

    The most widely spread eating habit is characterized by a reduced intake of dietary fiber, an increased intake of simple sugars, a high intake of refined grain products, an altered fat composition of the diet, and a dietary pattern characterized by a high glycemic load, an increased body weight and reduced physical activity. In this chapter the effects of this eating pattern on disease risk will be outlined. There are no epidemiological studies showing that the increase of glucose, fructose or sucrose intake is directly and independently associated with an increased risk of atherosclerosis or coronary heart disease (CHD). On the other hand a large number of studies has reported a reduction of fatal and non-fatal CHD events as a function of the intake of complex carbohydrates--respectively 'dietary fiber' or selected fiber-rich food (e.g., whole grain cereals). It seems that eating too much 'fast' carbohydrate [i.e., carbohydrates with a high glycemic index (GI)] may have deleterious long-term consequences. Indeed the last decades have shown that a low fat (and consecutively high carbohydrate) diet alone is not the best strategy to combat modern diseases including atherosclerosis. Quantity and quality issues in carbohydrate nutrient content are as important as they are for fat. Multiple lines of evidence suggest that for cardiovascular disease prevention a high sugar intake should be avoided. There is growing evidence of the high impact of dietary fiber and foods with a low GI on single risk factors (e.g., lipid pattern, diabetes, inflammation, endothelial function etc.) as well as also the development of the endpoints of atherosclerosis especially CHD. PMID:16596802

  14. Tumor-associated macrophages promote tumor cell proliferation in nasopharyngeal NK/T-cell lymphoma

    OpenAIRE

    Liu, Yixiong; Fan, Linni; Wang, Yingmei; Li, Peifeng; Zhu, Jin; Wang, Lu; Zhang, Weichen; Zhang, Yuehua; Huang, Gaosheng

    2014-01-01

    Objective: To explore the relationship between the number of tumor-associated macrophages (TAMs) and proliferative activity of tumor cells and the relationship between two macrophage biomarkers CD68 and CD163 in nasopharyngeal NK/T-cell lymphoma. Methods: Immunohistochemistry was used to reconfirm the diagnosis of nasal NK/T-cell lymphoma and detect the numbers of TAMs and the ki-67 label index of the tumor cells in all 31 cases. In addition, 12 cases of inflammatory cases were collected as c...

  15. Distinctive role of activated tumor-associated macrophages in photosensitizer accumulation

    Science.gov (United States)

    Korbelik, Mladen; Krosl, Gorazd

    1995-05-01

    Cells dissociated from tumors (carcinomas and sarcomas) growing subcutaneously in mice that have been administered Photofrin or other photosensitizers were analyzed by flow cytometry. Monoclonal antibodies were used for identification of major cellular populations contained in these tumors. The results demonstrate that a subpopulation of tumor-associated macrophages (TAMs) is unique among tumor cell populations in that it excels in the accumulation of very high levels of photosensitizers. These macrophages showed an increased expression of interleukin 2 receptor, which is indicative of their activated state. since macrophages were reported to concentrate in the periphery of human neoplasms, it is suggested that activates TAMs are the determinants of tumor-localized photosensitizer fluorescence.

  16. Signaling Circuits and Regulation of Immune Suppression by Ovarian Tumor-Associated Macrophages

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    Martin J. Cannon

    2015-05-01

    Full Text Available The barriers presented by immune suppression in the ovarian tumor microenvironment present one of the biggest challenges to development of successful tumor vaccine strategies for prevention of disease recurrence and progression following primary surgery and chemotherapy. New insights gained over the last decade have revealed multiple mechanisms of immune regulation, with ovarian tumor-associated macrophages/DC likely to fulfill a central role in creating a highly immunosuppressive milieu that supports disease progression and blocks anti-tumor immunity. This review provides an appraisal of some of the key signaling pathways that may contribute to immune suppression in ovarian cancer, with a particular focus on the potential involvement of the c-KIT/PI3K/AKT, wnt/β-catenin, IL-6/STAT3 and AhR signaling pathways in regulation of indoleamine 2,3-dioxygenase expression in tumor-associated macrophages. Knowledge of intercellular and intracellular circuits that shape immune suppression may afford insights for development of adjuvant treatments that alleviate immunosuppression in the tumor microenvironment and enhance the clinical efficacy of ovarian tumor vaccines.

  17. [Carbohydrates and fiber].

    Science.gov (United States)

    Lajolo, F M; de Menezes, E W; Filisetti-Cozzi, T M

    1988-09-01

    Dietary carbohydrates comprise two fractions that may be classified as digestible, and which are useful as energy sources (simple and complex carbohydrates) and fiber, which is presumed to be of no use to the human body. There are insufficient epidemiologic data on the metabolic effects of simple carbohydrates and it is not advisable to make quantitative recommendations of intake. It is questionable to recommend in developing countries that a fixed proportion of dietary energy be derived from simple sugars, due to the high prevalence of deficient energy intake, cultural habits, and regional differences in food intake and physical activity. In relation to recommendations of complex carbohydrates, it should be considered that their absorption is influenced by many factors inherent to the individual and to the foods. Fiber is defined as a series of different substances derived from tissue structures, cellular residues and undigested chemical substances that may be partially utilized after intestinal bacteria have acted on them. There is not a clear definition of the chemical composition of fiber, but it consists mainly of polysaccharides (such as cellulose, hemicellulose and pectins), lignin and end products of the interactions of various food components. The effects of fiber, such as control of food intake, regulation of gastrointestinal transit, post-prandial blood concentrations of cholesterol, glucose and insulin, flatulence and alterations in nutrient bioavailability are due to various physical properties inherent to its chemical components. Impairment of nutrient absorption may be harmful, mainly among populations whose food intake is lower than their energy needs, and with a high fiber content. This may be particularly important in pregnant women, growing children and the elderly, and should be considered when making nutrient recommendations. A precise knowledge of fiber is also important to calculate the real energy value of foods, mainly for two reasons: 1

  18. ONCOLYTIC VIRUS-MEDIATED REVERSAL OF IMPAIRED TUMOR ANTIGEN PRESENTATION

    Directory of Open Access Journals (Sweden)

    Shashi Ashok Gujar

    2014-04-01

    Full Text Available Anti-tumor immunity can eliminate existing cancer cells and also maintain a constant surveillance against possible relapse. Such an antigen-specific adaptive response begins when tumor-specific T cells become activated. T cell activation requires two signals on antigen presenting cells (APCs: antigen presentation through MHC molecules and co-stimulation. In the absence of one or both of these signals, T cells remain inactivated or can even become tolerized. Cancer cells and their associated microenvironment strategically hinder the processing and presentation of tumor antigens and consequently prevent the development of anti-tumor immunity. Many studies, however, demonstrate that interventions that overturn tumor-associated immune evasion mechanisms can establish anti-tumor immune responses of therapeutic potential. One such intervention is oncolytic virus (OV-based anti-cancer therapy. Here we discuss how OV-induced immunological events override tumor-associated antigen presentation impairment and promote appropriate T cell:APC interaction. Detailed understanding of this phenomenon is pivotal for devising the strategies that will enhance the efficacy of OV-based anti-cancer therapy by complementing its inherent oncolytic

  19. The role of carbohydrates in infection strategies of enteric pathogens.

    Science.gov (United States)

    Kato, Kentaro; Ishiwa, Akiko

    2015-03-01

    Enteric pathogens cause considerable public health concerns worldwide including tropical regions. Here, we review the roles of carbohydrates in the infection strategies of various enteric pathogens including viruses, bacteria and protozoa, which infect the epithelial lining of the human and animal intestine. At host cell entry, enteric viruses, including norovirus, recognize mainly histo-blood group antigens. At the initial step of bacterial infections, carbohydrates also function as receptors for attachment. Here, we describe the function of carbohydrates in infection by Salmonella enterica and several bacterial species that produce a variety of fimbrial adhesions. During invasion by enteropathogenic protozoa, apicomplexan parasites utilize sialic acids or sulfated glycans. Carbohydrates serve as receptors for infection by these microbes; however, their usage of carbohydrates varies depending on the microbe. On the surface of the mucosal tissues of the gastrointestinal tract, various carbohydrate moieties are present and play a crucial role in infection, representing the site of infection or route of access for most microbes. During the infection and/or invasion process of the microbes, carbohydrates function as receptors for various microbes, but they can also function as a barrier to infection. One approach to develop effective prophylactic and therapeutic antimicrobial agents is to modify the drug structure. Another approach is to modify the mode of inhibition of infection depending on the individual pathogen by using and mimicking the interactions with carbohydrates. In addition, similarities in mode of infection may also be utilized. Our findings will be useful in the development of new drugs for the treatment of enteric pathogens. PMID:25859152

  20. The Tumor-Associated Marker, PVRL4 (Nectin-4, Is the Epithelial Receptor for Morbilliviruses

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    Sebastien Delpeut

    2014-06-01

    Full Text Available PVRL4 (nectin-4 was recently identified as the epithelial receptor for members of the Morbillivirus genus, including measles virus, canine distemper virus and peste des petits ruminants virus. Here, we describe the role of PVRL4 in morbillivirus pathogenesis and its promising use in cancer therapies. This discovery establishes a new paradigm for the spread of virus from lymphocytes to airway epithelial cells and its subsequent release into the environment. Measles virus vaccine strains have emerged as a promising oncolytic platform for cancer therapy in the last ten years. Given that PVRL4 is a well-known tumor-associated marker for several adenocarcinoma (lung, breast and ovary, the measles virus could potentially be used to specifically target, infect and destroy cancers expressing PVRL4.

  1. The tumor-associated marker, PVRL4 (nectin-4), is the epithelial receptor for morbilliviruses.

    Science.gov (United States)

    Delpeut, Sebastien; Noyce, Ryan S; Richardson, Christopher D

    2014-06-01

    PVRL4 (nectin-4) was recently identified as the epithelial receptor for members of the Morbillivirus genus, including measles virus, canine distemper virus and peste des petits ruminants virus. Here, we describe the role of PVRL4 in morbillivirus pathogenesis and its promising use in cancer therapies. This discovery establishes a new paradigm for the spread of virus from lymphocytes to airway epithelial cells and its subsequent release into the environment. Measles virus vaccine strains have emerged as a promising oncolytic platform for cancer therapy in the last ten years. Given that PVRL4 is a well-known tumor-associated marker for several adenocarcinoma (lung, breast and ovary), the measles virus could potentially be used to specifically target, infect and destroy cancers expressing PVRL4. PMID:24892636

  2. Ghost cell odontogenic tumor associated with odontoma--report of two rare cases.

    Science.gov (United States)

    Hogge, Maritzabel; Velez, Ines; Kaltman, Steven; Movahed, Reza; Yeh, Frank

    2012-01-01

    The ghost cell odontogenic tumor (GCOT) is a neoplastic/cystic lesion with a diverse histopathological and clinical behavior It was formerly known as calcified odontogenic cyst, but in 2005 the World Health Organization categorized this lesion as an odontogenic, benign tumor rather than a cyst; nominating this neoplasm as calcifying cystic odontogenic tumor. A later comprehensive classification named it ghost cell odontogenic tumor because the most remarkable histopathologic characteristic is the presence of a mass of ghost cells embedded in the epithelium. We report two cases of a rare variant of a ghost cell odontogenic tumor associated with odontoma; to our knowledge, one is the youngest patient (four month old) reported in the English literature.

  3. Tumor-Derived CXCL1 Promotes Lung Cancer Growth via Recruitment of Tumor-Associated Neutrophils

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    Ming Yuan

    2016-01-01

    Full Text Available Neutrophils have a traditional role in inflammatory process and act as the first line of defense against infections. Although their contribution to tumorigenesis and progression is still controversial, accumulating evidence recently has demonstrated that tumor-associated neutrophils (TANs play a key role in multiple aspects of cancer biology. Here, we detected that chemokine CXCL1 was dramatically elevated in serum from 3LL tumor-bearing mice. In vitro, 3LL cells constitutively expressed and secreted higher level of CXCL1. Furthermore, knocking down CXCL1 expression in 3LL cells significantly hindered tumor growth by inhibiting recruitment of neutrophils from peripheral blood into tumor tissues. Additionally, tumor-infiltrated neutrophils expressed higher levels of MPO and Fas/FasL, which may be involved in TAN-mediated inhibition of CD4+ and CD8+ T cells. These results demonstrate that tumor-derived CXCL1 contributes to TANs infiltration in lung cancer which promotes tumor growth.

  4. Studies on mechanism of Sialy Lewis-X antigen in liver metastases of human colorectal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao Wei Li; Yan Qing Ding; Jun Jie Cai; Shao Qing Yang; Lian Bing An; Dong Fang Qiao

    2001-01-01

    @@INTRODUCTION Sialyl Lewis-X antigen ,correlated with carcinoma, is a group of carbohydrate antigen containing oligosaccharide expressed of embryonic tisue and glycoproteins on cell surface of embryonic tissue[1].The SLeX antigen located on cell surface is synthesized principally by two enzymes ,al ,3fucosyltransfrease and a2, 3sialyctransferase.In adults ,SLeX antigen is expressed principally on the surfaces of granulocytic cells and some tumor cells .

  5. Effects of Carbohydrate Consumption Case Study: carbohydrates in Bread

    Directory of Open Access Journals (Sweden)

    Neacsu N.A.

    2014-12-01

    Full Text Available Carbohydrates perform numerous roles in living organisms; they are an important source of energy. The body uses carbohydrates to make glucose which is the fuel that gives it energy and helps keep everything going. However, excess carbohydrate consumption has negative health effects. Bread is a basic product in our nutrition and it also is a product with a high content of carbohydrates. So, it is important to find out more information on bread and on the recommended bread type best for consumption.

  6. The role of carbohydrate in determining the immunochemical properties of the hemagglutinin of influenza A virus

    International Nuclear Information System (INIS)

    Most of the carbohydrate was removed from influenza with MRC II (H3N2) and its purified hemagglutinin (HA) on treatment with glycosidases, including α-mannosidase, #betta#-N-acetylglucosaminidase, #betta#-galactosidase and α-fucosidase. The release of 50 per cent of the carbohydrate from intact virus particles significantly affected hemagglutinating activity. The ability of untreated and glycosidase-treated virus to inhibit the binding of antibodies directed against the hemagglutinin was almost indistinguishable by competitive radioimmunoassay (RIA). Up to 60 per cent of the carbohydrate from the purified HA of influenza virus could be removed. The antigenicity of glycosidase treated HA molecules decreased 8-fold compared to intact HAs as measured by competitive RIA. In addition, glycosidase digestion of 125I-labeled HA resulted in a decrease in its reactivity in direct RIA. We conclude that the carbohydrate portion of the HA of influenza virus is not of major importance in defining the antigenicity of HA. (Author)

  7. Synthesis and inhibition potency of novel ureido benzenesulfonamides incorporating GABA as tumor-associated carbonic anhydrase IX and XII inhibitors.

    Science.gov (United States)

    Ceruso, Mariangela; Antel, Sabrina; Scozzafava, Andrea; Supuran, Claudiu T

    2016-01-01

    New ureido benzenesulfonamides incorporating a GABA moiety as a linker between the ureido and the sulfonamide functionalities were synthesized and their inhibition potency determined against both the predominant cytosolic (hCA I and II) and the transmembrane tumor-associated (hCA IX and XII) isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The majority of these compounds were medium potency inhibitors of the cytosolic isoform hCA I and effective hCA II inhibitors, whereas they showed strong inhibition of the two transmembrane tumor-associated isoforms hCA IX and XII, with KIs in nanomolar range. Only one derivative had a good selectivity for inhibition of the tumor-associated hCA IX target isoform over the cytosolic and physiologically dominant off-target hCA I and II, being thus a potential tool to develop new anticancer agents. PMID:25792500

  8. Impact of Dietary Carbohydrate and Protein Levels on Carbohydrate Metabolism

    Science.gov (United States)

    Lasker, Denise Ann

    2009-01-01

    The goal of this dissertation was to investigate the impact of changing dietary carbohydrate (CARB) intakes within recommended dietary guidelines on metabolic outcomes specifically associated with glycemic regulations and carbohydrate metabolism. This research utilized both human and animal studies to examine changes in metabolism across a wide…

  9. Expression of Lewisa, Sialyl Lewisa, Lewisx, Sialyl Lewisx, Antigens as Prognostic Factors in Patients with Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Tohru Nakagoe

    2000-01-01

    Full Text Available BACKGROUND: Altered expression of blood group-related carbohydrate antigens such as sialyl Lewis (Lex antigen in tumours is associated with tumour progression behaviour and subsequent prognosis. However, the prognostic value of the expression of Le-related antigens in colorectal tumours remains unclear.

  10. Carbohydrates and Diabetes (For Parents)

    Science.gov (United States)

    ... of diet foods. These foods may contain extra sugar as a substitute for fat calories. Try to include your child or teen as you evaluate and select healthy carbohydrate-containing foods. With ... blood sugar. By taking a smart approach to balancing carbohydrates, ...

  11. MUC-1 Tumor Antigen Agonist Epitopes for Enhancing T-cell Responses to Human Tumors | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    Scientists at NIH have identified 7 new agonist epitopes of the MUC-1 tumor associated antigen. Compared to their native epitope counterparts, peptides reflecting these agonist epitopes have been shown to enhance the generation of human tumor cells, which in turn have a greater ability to kill human tumor cells endogenously expressing the native MUC-1 epitope.

  12. Gene expression down-regulation in CD90+ prostate tumor-associated stromal cells involves potential organ-specific genes

    International Nuclear Information System (INIS)

    The prostate stroma is a key mediator of epithelial differentiation and development, and potentially plays a role in the initiation and progression of prostate cancer. The tumor-associated stroma is marked by increased expression of CD90/THY1. Isolation and characterization of these stromal cells could provide valuable insight into the biology of the tumor microenvironment. Prostate CD90+ stromal fibromuscular cells from tumor specimens were isolated by cell-sorting and analyzed by DNA microarray. Dataset analysis was used to compare gene expression between histologically normal and tumor-associated stromal cells. For comparison, stromal cells were also isolated and analyzed from the urinary bladder. The tumor-associated stromal cells were found to have decreased expression of genes involved in smooth muscle differentiation, and those detected in prostate but not bladder. Other differential expression between the stromal cell types included that of the CXC-chemokine genes. CD90+ prostate tumor-associated stromal cells differed from their normal counterpart in expression of multiple genes, some of which are potentially involved in organ development

  13. Incidental intraoperative discovery of a pancreatic neuroendocrine tumor associated with chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Surlin Valeriu

    2012-09-01

    Full Text Available Abstract Pancreatic neuroendocrine tumors are a rare entity with an incidence between 2 per million to 5 per 100 000. Association with pancreatitis (acute or chronic is rare and is considered to be determined by the tumoral obstruction of pancreatic ducts, but sometimes occurs without any apparent relationship between them. Non-functional neuroendocrine pancreatic tumors are usually diagnosed when either very large or metastatic. Small ones are occasionally diagnosed when imagery is performed for other diagnostic reasons. Intraoperative discovery is even rarer and poses problems of differential diagnosis with other pancreatic tumors. Association with chronic pancreatitis is rare and usually due to pancreatic duct obstruction by the tumor. We describe the case of a patient with a small non-functioning neuroendocrine tumor in the pancreatic tail accidentally discovered during surgery for delayed traumatic splenic rupture associated with chronic alcoholic pancreatitis. The tumor of 1.5cm size was well differentiated and confined to the pancreas, and was resected by a distal splenopancreatectomy. Conclusions Surgeons should be well aware of the rare possibility of a non-functional neuroendocrine tumor in the pancreas, associated with chronic pancreatitis, surgical resection being the optimal treatment for cure. Histopathology is of utmost importance to establish the correct diagnosis, grade of differentiation, malignancy and prognosis. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2114470176676003.

  14. Behavior of Endogenous Tumor-Associated Macrophages Assessed In Vivo Using a Functionalized Nanoparticle

    Directory of Open Access Journals (Sweden)

    Antoine Leimgruber

    2009-05-01

    Full Text Available Tumor-associated macrophages (TAMs invade the tumor stroma in many cancers, yet their role is incompletely understood. To visualize and better understand these critical cells in tumor progression, we screened a portfolio of rationally selected, injectable agents to image endogenous TAMs ubiquitously in three different cancer models (colon carcinoma, lung adenocarcinoma, and soft tissue sarcoma. AMTA680, a functionally derivatized magneto-fluorescent nanoparticle, labeled a subset of myeloid cells with an “M2” macrophage phenotype, whereas other neighboring cells, including tumor cells and a variety of other leukocytes, remained unlabeled. We further show that AMTA680-labeled endogenous TAMs are not altered and can be tracked noninvasively at different resolutions and using various imaging modalities, e.g., fluorescence molecular tomography, magnetic resonance imaging, and multiphoton and confocal intravital microscopy. Quantitative assessment of TAM distribution and activity in vivo identified that these cells cluster in delimited foci within tumors, show relatively low motility, and extend cytoplasmic protrusions for prolonged physical interactions with neighboring tumor cells. Noninvasive imaging can also be used to monitor TAM-depleting regimen quantitatively. Thus, AMTA680 or related cell-targeting agents represent appropriate injectable vehicles for in vivo analysis of the tumor microenvironment.

  15. Tumor-associated neutrophils stimulate T cell responses in early-stage human lung cancer

    Science.gov (United States)

    Eruslanov, Evgeniy B.; Bhojnagarwala, Pratik S.; Quatromoni, Jon G.; Stephen, Tom Li; Ranganathan, Anjana; Deshpande, Charuhas; Akimova, Tatiana; Vachani, Anil; Litzky, Leslie; Hancock, Wayne W.; Conejo-Garcia, José R.; Feldman, Michael; Albelda, Steven M.; Singhal, Sunil

    2014-01-01

    Infiltrating inflammatory cells are highly prevalent within the tumor microenvironment and mediate many processes associated with tumor progression; however, the contribution of specific populations remains unclear. For example, the nature and function of tumor-associated neutrophils (TANs) in the cancer microenvironment is largely unknown. The goal of this study was to provide a phenotypic and functional characterization of TANs in surgically resected lung cancer patients. We found that TANs constituted 5%–25% of cells isolated from the digested human lung tumors. Compared with blood neutrophils, TANs displayed an activated phenotype (CD62LloCD54hi) with a distinct repertoire of chemokine receptors that included CCR5, CCR7, CXCR3, and CXCR4. TANs produced substantial quantities of the proinflammatory factors MCP-1, IL-8, MIP-1α, and IL-6, as well as the antiinflammatory IL-1R antagonist. Functionally, both TANs and neutrophils isolated from distant nonmalignant lung tissue were able to stimulate T cell proliferation and IFN-γ release. Cross-talk between TANs and activated T cells led to substantial upregulation of CD54, CD86, OX40L, and 4-1BBL costimulatory molecules on the neutrophil surface, which bolstered T cell proliferation in a positive-feedback loop. Together our results demonstrate that in the earliest stages of lung cancer, TANs are not immunosuppressive, but rather stimulate T cell responses. PMID:25384214

  16. Identification of the differential expressive tumor associated genes in rectal cancers by cDNA microarray

    Institute of Scientific and Technical Information of China (English)

    Xue-Qin Gao; Jin-Xiang Han; Zhong-Fa Xu; Wei-Dong Zhang; Hua-Ning Zhang; Hai-Yan Huang

    2007-01-01

    AIM: To identify tumor associated genes of rectal cancer and to probe the application possibility of gene expression profiles for the classification of tumors.METHODS: Rectal cancer tissues and their paired normal mucosa were obtained from patients undergoing surgical resection of rectal cancer. Total RNA was extracted using Trizol reagents. First strand cDNA synthesis was indirectly labeled with aminoallyl-dUTP and coupled with Cy3 or Cy5 dye NHS mono-functional ester. After normalization to total spots, the genes which background subtracted intensity did not exceed 2 SD above the mean blank were excluded. The data were then sorted to obtain genes differentially expressed by≥ 2 fold up or down in at least 5 of the 21 patients.RESULTS: In the 21 rectal cancer patients, 23 genes were up-regulated in at least 5 samples and 15 genes were down-regulated in at least 5 patients. Hierachical cluster analysis classified the patients into two groups according to the clinicopathological stage, with one group being all above stage Ⅱ and one group all below stage Ⅱ.CONCLUSION: The up-regulated genes and downregulated genes may be molecular markers of rectal cancer. The expression profiles can be used for classification of rectal cancer.

  17. Tumor-Associated Macrophages as Major Players in the Tumor Microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Chanmee, Theerawut [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Ontong, Pawared [Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Konno, Kenjiro [Department of Animal Medical Sciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Itano, Naoki, E-mail: itanon@cc.kyoto-su.ac.jp [Institute of Advanced Technology, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Division of Engineering (Biotechnology), Graduate School of Engineering, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan); Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kita-ku, Kyoto 603-8555 (Japan)

    2014-08-13

    During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. Macrophages shift their functional phenotypes in response to various microenvironmental signals generated from tumor and stromal cells. Based on their function, macrophages are divided broadly into two categories: classical M1 and alternative M2 macrophages. The M1 macrophage is involved in the inflammatory response, pathogen clearance, and antitumor immunity. In contrast, the M2 macrophage influences an anti-inflammatory response, wound healing, and pro-tumorigenic properties. Tumor-associated macrophages (TAMs) closely resemble the M2-polarized macrophages and are critical modulators of the tumor microenvironment. Clinicopathological studies have suggested that TAM accumulation in tumors correlates with a poor clinical outcome. Consistent with that evidence, experimental and animal studies have supported the notion that TAMs can provide a favorable microenvironment to promote tumor development and progression. In this review article, we present an overview of mechanisms responsible for TAM recruitment and highlight the roles of TAMs in the regulation of tumor angiogenesis, invasion, metastasis, immunosuppression, and chemotherapeutic resistance. Finally, we discuss TAM-targeting therapy as a promising novel strategy for an indirect cancer therapy.

  18. Characterization of Truncated Tumor-Associated NADH Oxidase (ttNOX)

    Science.gov (United States)

    Karr, Laurel J.; Malone, Christine C.; Burk, Melissa; Moore, Blake P.; Achari, Aniruddha; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Bacterial, plant and animal cells possess novel surface proteins that exhibit both NADH oxidation (NOX) or hydroquinone and protein disulfide-thiol interchange. These enzymatic activities alternate to yield oscillating patterns wjth period lengths of approximately 24 minutes. The catalytic period of NOX proteins are temperature compensated and gravity responsive. We report the cloning, expression and characterization of truncated tumor-associated NADH oxidase (ttNOX), in which the membrane spanning region has been deleted. The cDNA (originated from HeLa cells) was cloned into pET-34b and pET-14b (Novagen) vectors for E. coli expression. Optimized expression and purification protocols yielded greater than 300mg per liter of culture with greater than 95% purity. Circular dichroism data was collected from a 2.7mg/ml solution in a 0.1mm cuvette with variable scanning using an Olis RSM CD spectrophotometer. The ellipticity values were scanned from 190 to 260nm. The spectra recorded have characteristics for alpha proteins with band maxima at 216nm and a possible shoulder at 212nm at 12OC and 250 C. Protein crystal screens are in progress and, to date, only small crystals have been observed. The regular periodic oscillatory change in the ttNOX protein is indicative of a possible time-keeping functional role. A single protein possessing alternating catalytic activities, with a potential biological clock function, is unprecedented and structural determination is paramount to understanding this role.

  19. Tumor-Associated Macrophages as Incessant Builders and Destroyers of the Cancer Stroma

    Energy Technology Data Exchange (ETDEWEB)

    Liguori, Manuela; Solinas, Graziella; Germano, Giovanni [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy); Mantovani, Alberto [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy); Department of Translational Medicine, University of Milano, Milano 20089 (Italy); Allavena, Paola, E-mail: paola.allavena@humanitasresearch.it [Department of Immunology and Inflammation Istituto Clinico Humanitas, Via Manzoni 113, Rozzano-Milano 20089 (Italy)

    2011-09-28

    Tumor-Associated Macrophages (TAM) are key components of the reactive stroma of tumors. In most, although not all cancers, their presence is associated with poor patient prognosis. In addition to releasing cytokines and growth factors for tumor and endothelial cells, a distinguished feature of TAM is their high-rate degradation of the extra-cellular matrix. This incessant stroma remodelling favours the release of matrix-bound growth factors and promotes tumor cell motility and invasion. In addition, TAM produce matrix proteins, some of which are typical of the neoplastic tissues. The gene expression profile of TAM isolated from human tumors reveals a matrix-related signature with the up-regulation of genes coding for different matrix proteins, as well as several proteolytic enzymes. Among ECM components are: osteopontin, osteoactivin, collagens and fibronectin, including also a truncated isoform of fibronectin termed migration stimulation factor. In addition to serve as structural proteins, these matrix components have key functions in the regulation of the vessel network, in the inductionof tumor cell motility and degradation of cellular debris. Among proteolytic enzymes are: matrix metalloproteases, cathepsins, lysosomal and ADAM proteases, and the urokinase-type plasminogen activator. The degrading activity of TAM, coupled to the production of bio-active ECM proteins, co-operate to the build-up and maintenance of an inflammatory micro-environment which eventually promotes tumor progression.

  20. Depletion of tumor associated macrophages slows the growth of chemically-induced mouse lung adenocarcinomas

    Directory of Open Access Journals (Sweden)

    Jason M. Fritz

    2014-11-01

    Full Text Available Chronic inflammation is a risk factor for lung cancer, and low dose aspirin intake reduces lung cancer risk. However, the roles that specific inflammatory cells and their products play in lung carcinogenesis have yet to be fully elucidated. In mice, alveolar macrophage numbers increase as lung tumors progress, and pulmonary macrophage programming changes within 2 weeks of carcinogen exposure. To examine how macrophages specifically affect lung tumor progression, they were depleted in mice bearing urethane-induced lung tumors using clodronate-encapsulated liposomes. Alveolar macrophage populations decreased to ≤ 50% of control levels after 4-6 weeks of liposomal clodronate treatment. Tumor burden decreased by 50% compared to vehicle treated mice, and tumor cell proliferation, as measured by Ki67 staining, was also attenuated. Pulmonary fluid levels of IGF-I, CXCL1, IL-6 and CCL2 diminished with clodronate liposome treatment. Tumor associated macrophages expressed markers of both M1 and M2 programming in vehicle and clodronate liposome treated mice. Mice lacking CCR2 (the receptor for macrophage chemotactic factor CCL2 had comparable numbers of alveolar macrophages and showed no difference in tumor growth rates when compared to similarly treated wild-type mice suggesting that while CCL2 may recruit macrophages to lung tumor microenvironments, redundant pathways can compensate when CCL2/CCR2 signaling is inactivated. Depletion of pulmonary macrophages rather than inhibition of their recruitment may be an advantageous strategy for attenuating lung cancer progression.

  1. Tumor-associated macrophages: a novel potential target for cancer treatment

    Institute of Scientific and Technical Information of China (English)

    YUE Zhi-qiang; LIU Yu-ping; RUAN Jun-shan; ZHOU Liang; LU Yin

    2012-01-01

    Special emphasis about cancer metastasis was concentrated on tumor cells themselves,and we usually considered the ability of migration and invasion was the final decider.Recently,bewaring of tumor microenvironment is a fundamental determinant in metastasis has become the most outstanding breakthrough.Considerable “microbes” in the microenvironment are closely linked with tumor metastatic behaviors,and the major proportion of them is tumor-associated macrophages (TAMs).Actually,TAMs conserve immediate “cross-talk” with cancer cells throughout tumor development.It is generally accepted that TAMs have mostly pro-tumoral functions and play an important role in several stages of tumor progression.This progression involves a series of events that leads from the primary site to the metastatic site,including tumor cell growth,angiogenesis,migration,invasion,intravasation and finally extravasation at distant site where the process begins again (metastasis).Thereby,TAMs has attracted substantial attentions in recent years and could become a promising therapeutic strategy.In this review,we focus on the multi-functions of TAMs in cancer and certain drugs targeting TAMs for cancer treatment those are under experimental research procedures or have even been entered human clinical tests.

  2. miR-511-3p Modulates Genetic Programs of Tumor-Associated Macrophages

    Directory of Open Access Journals (Sweden)

    Mario Leonardo Squadrito

    2012-02-01

    Full Text Available Expression of the mannose receptor (MRC1/CD206 identifies macrophage subtypes, such as alternatively activated macrophages (AAMs and M2-polarized tumor-associated macrophages (TAMs, which are endowed with tissue-remodeling, proangiogenic, and protumoral activity. However, the significance of MRC1 expression for TAM's protumoral activity is unclear. Here, we describe and characterize miR-511-3p, an intronic microRNA (miRNA encoded by both mouse and human MRC1 genes. By using sensitive miRNA reporter vectors, we demonstrate robust expression and bioactivity of miR-511-3p in MRC1+ AAMs and TAMs. Unexpectedly, enforced expression of miR-511-3p tuned down the protumoral gene signature of MRC1+ TAMs and inhibited tumor growth. Our findings suggest that transcriptional activation of Mrc1 in TAMs evokes a genetic program orchestrated by miR-511-3p, which limits rather than enhances their protumoral functions. Besides uncovering a role for MRC1 as gatekeeper of TAM's protumoral genetic programs, these observations suggest that endogenous miRNAs may operate to establish thresholds for inflammatory cell activation in tumors.

  3. CHARACTER OF TUMOR ASSOCIATED PROTEIN RECOGNIZED BY MONOCLONAL ANTIBODY AGAINST YUNNAN GEJIU LUNG CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objectives: To identify and characterize lung cancer associated protein N35 and attempt to learn the prospective possibility of the clinical application of the protein N35. Methods: Immunoprecipitation, immunoblotting, differential centrifigation and subcellular assay, immunohistochemistry, N-glycanase digestion, mitotic cell immunoflourescence and multiple methods of affinity chromatography have been used with the monoclonal antibody N-35 to detect the distribution of the protein N35 among the various cancer cell lines and normal human tissue, the relationship between the protein N35 and glycoprotein, the location of the subcellular structure and chromosomal domain of the protein N35,the most effective way of purification of tumor associated protein N35. Results: The protein N35 is a glycoprotein, distributes to the human lung cancer cell line GLC-82, human cervical cancer cell line Hela, human hepatic cancer cell line HepG-2 and human breast cancer cell line PMC with different relative molecular mass(Mr), but no expression of the protein ingredient in normal human fresh tissue; concentrates at the nuclei significantly ,much more than at the mitochondrail and membrane, locates at the centriole of the chromosomal domain. Conclusions: The lung cancer associated protein N35 might be expressed only by the cancer cells and related with the proliferation of cancer cells as a role of tumor cell growth regulator.

  4. Oral carbohydrate loading with 18% carbohydrate beverage alleviates insulin resistance.

    Science.gov (United States)

    Tamura, Takahiko; Yatabe, Tomoaki; Kitagawa, Hiroyuki; Yamashita, Koichi; Hanazaki, Kazuhiro; Yokoyama, Masataka

    2013-01-01

    Preoperative 12.6% oral carbohydrate loading is an element of the Enhanced Recovery After Surgery (ERAS) protocol aimed at alleviating postoperative insulin resistance; however, in Japan, beverages with 18% carbohydrate content are generally used for preoperative carbohydrate loading. We investigated the effect of 18% carbohydrate loading on alleviating insulin resistance. Six healthy volunteers participated in this crossover-randomized study and were segregated into 2 groups: volunteers in the carbohydrate-loading group (group A) who fasted from after 9 pm and ingested 375 mL of a beverage containing 18% carbohydrate (ArginaidWaterTM; Nestle, Tokyo, Japan) between 9 pm and 12 pm, and 250 mL of the same liquid at 6:30 am. Volunteers in control group (group B) drank only water. At 8:30 am, a hyperinsulinemic normoglycemic clamp was initiated. Glucose infusion rate (GIR) and levels of ketone bodies and cytokines (IL-1β, IL-6, and TNF-α) before clamping were evaluated. p<0.05 was considered statistically significant. Levels of blood glucose, insulin, and cytokines at the start of the clamp were similar in both the groups. The GIR in group A was significantly higher than that in group B (11.5±2.4 vs 6.2±2.2 mg/kg/min, p=0.005), while blood ketone body levels were significantly lower in group A (22±4 vs 124±119 μmol/L, p=0.04). Preoperative 18% carbohydrate loading could prevent the decrease in insulin sensitivity and suppress catabolism in healthy volunteers. Thus, carbohydrate loading with a beverage with 18% carbohydrate content might contribute to improvements in perioperative management. PMID:23353610

  5. Diagnostic value of tumor markers carbohydrate antigen 125 and alpha fetal protein for immature and mature ovarian teratomas%肿瘤标志物糖类抗原125、甲胎蛋白对卵巢未成熟畸胎瘤及成熟畸胎瘤的诊断价值

    Institute of Scientific and Technical Information of China (English)

    李水莲

    2013-01-01

    目的 探讨血清肿瘤标志物糖类抗原(CA)125、甲胎蛋白(AFP)联合检测对卵巢未成熟畸胎瘤及成熟畸胎瘤的诊断价值.方法 回顾性分析本院妇科初治经病理证实的111例卵巢畸胎瘤患者的临床资料,统计分析血清CA125、AFP单项,并联合检测其在卵巢未成熟畸胎瘤、成熟畸胎瘤中的差异.结果 未成熟组术前血清CA125、AFP水平以及CA125、AFP阳性率均显著高于成熟组.应用单项检测时,CA125对卵巢未成熟畸胎瘤的灵敏度较高,达43.75%,AFP的特异度及总正确率较高,特异度可达100%,但灵敏度较低.联合检测较单一指标明显提高了诊断的灵敏度,但特异度有所下降.结论 血清肿瘤标志物CA125、AFP联合检测对卵巢未成熟畸胎瘤及成熟畸胎瘤的诊断、鉴别诊断有一定参考价值,对临床医师选择手术方式有较大帮助.%Objective To explore the diagnostic value of joint detection of serum tumor markers carbohydrate antigen 125 (CA125) and alpha fetal protein (AFP) for immature and mature ovarian teratomas. Methods The clinical data of 111 patients with ovarian teratomas in our hospital were retrospectively analyzed. The single event of CA125 and AFP in serum was statistically analyzed, and the differences between immature and mature ovarian teratomas were jointly detected. Results The levels of serum CA125 and AFP and their positive rates in immature group before treatment were significantly higher than those in mature group. The sensitivity of CA125 to immature ovarian teratoma was higher by using single- event detection, up to 43. 75% . The specificity and total accuracy of AFP was higher, and the specificity could reach 100% , while the sensitivity was lower. Compared with single - event detection, joint detection obviously increased diagnostic sensitivity, but the specificity declined. Conclusion The joint detection of serum tumor markers CA125 and AFP has a certain reference value for the

  6. Experimental study on the feasibility of MR imaging for tumor-associated macrophages

    International Nuclear Information System (INIS)

    Objective: To explore the feasibility of MR imaging for tumor-associated macrophages. Methods: BALB/c mice and BALB/c (nu/nu) nude mice were randomly divided into 6 groups (before injection, 6, 24, 48, 72 hours and 7 days after injection) and 5 groups (before injection, 6, 24, 48 and 72 hours after injection) with each group of 3 animals, respectively. Macrophages (RAW 264.7) were incubated with HSA-IONPs (dopamine/HSA coating iron oxide nanoparticle) containing 20 μg Fe/ml for 24 hours. Then, 5 × 106 labeled macrophages were collected and injected into subcutaneous 4T1 tumor- bearing BALB/c mice and 22B tumor-bearing nude mice via tail vein. At different time points described above, all animals performed transverse and coronal T2-weighted MR scans using a 7.0 T MR imaging unit. After sacrifice at different time points, tumor, liver and other organs were removed and processed for histological examination. Cytotoxicity of HSA-IONPs were assayed by MTT test, Statistics analysis adopt SPSS 11.5, the differences among groups were analyzed by one-way ANOVA. The difference was regarded as statistically significant, when P0.05). There was a significant linear positive correlation between the labelled macrophage numbers and MR R2 values (r=0.99, P2WI surrounding the necrosis and cystic degeneration 6 hours after macrophage injection, with a signal reduction of 59.4%. The signal of tumor parenchyma showed no significant change, with signal reduction of 4.8%. Irregular low signal ring could be seen at the junction of necrosis and parenchyma area at 24 hours after injection, with a signal reduction of 46.8% and the signal loss was restored to 96.8% around the necrosis and cystic degeneration. In 22B tumor model, multiple small scattered foci of low signal intensity were presented on T2WI around the necrosis and cystic degeneration 6 hours after macrophage injection with a signal drop of 46.8% and reduced at 24 hours, 2, 3 or 7 days after macrophage injection, the morphology

  7. Functional assessment of population and tumor-associated APE1 protein variants.

    Directory of Open Access Journals (Sweden)

    Jennifer L Illuzzi

    Full Text Available Apurinic/apyrimidinic endonuclease 1 (APE1 is the predominant AP site repair enzyme in mammals. APE1 also maintains 3'-5' exonuclease and 3'-repair activities, and regulates transcription factor DNA binding through its REF-1 function. Since complete or severe APE1 deficiency leads to embryonic lethality and cell death, it has been hypothesized that APE1 protein variants with slightly impaired function will contribute to disease etiology. Our data indicate that except for the endometrial cancer-associated APE1 variant R237C, the polymorphic variants Q51H, I64V and D148E, the rare population variants G241R, P311S and A317V, and the tumor-associated variant P112L exhibit normal thermodynamic stability of protein folding; abasic endonuclease, 3'-5' exonuclease and REF-1 activities; coordination during the early steps of base excision repair; and intracellular distribution when expressed exogenously in HeLa cells. The R237C mutant displayed reduced AP-DNA complex stability, 3'-5' exonuclease activity and 3'-damage processing. Re-sequencing of the exonic regions of APE1 uncovered no novel amino acid substitutions in the 60 cancer cell lines of the NCI-60 panel, or in HeLa or T98G cancer cell lines; only the common D148E and Q51H variants were observed. Our results indicate that APE1 missense mutations are seemingly rare and that the cancer-associated R237C variant may represent a reduced-function susceptibility allele.

  8. Tumor-associated macrophages (TAMs form an interconnected cellular supportive network in anaplastic thyroid carcinoma.

    Directory of Open Access Journals (Sweden)

    Bernard Caillou

    Full Text Available BACKGROUND: A relationship between the increased density of tumor-associated macrophages (TAMs and decreased survival was recently reported in thyroid cancer patients. Among these tumors, anaplastic thyroid cancer (ATC is one of the most aggressive solid tumors in humans. TAMs (type M2 have been recognized as promoting tumor growth. The purpose of our study was to analyze with immunohistochemistry the presence of TAMs in a series of 27 ATC. METHODOLOGY/PRINCIPAL FINDINGS: Several macrophages markers such as NADPH oxidase complex NOX2-p22phox, CD163 and CD 68 were used. Immunostainings showed that TAMs represent more than 50% of nucleated cells in all ATCs. Moreover, these markers allowed the identification of elongated thin ramified cytoplasmic extensions, bestowing a "microglia-like" appearance on these cells which we termed "Ramified TAMs" (RTAMs. In contrast, cancer cells were totally negative. Cellular stroma was highly simplified since apart from cancer cells and blood vessels, RTAMs were the only other cellular component. RTAMs were evenly distributed and intermingled with cancer cells, and were in direct contact with other RTAMs via their ramifications. Moreover, RTAMs displayed strong immunostaining for connexin Cx43. Long chains of interconnected RTAMs arose from perivascular clusters and were dispersed within the tumor parenchyma. When expressed, the glucose transporter Glut1 was found in RTAMs and blood vessels, but rarely in cancer cells. CONCLUSION: ATCs display a very dense network of interconnected RTAMs in direct contact with intermingled cancer cells. To our knowledge this is the first time that such a network is described in a malignant tumor. This network was found in all our studied cases and appeared specific to ATC, since it was not found in differentiated thyroid cancers specimens. Taken together, these results suggest that RTAMs network is directly related to the aggressiveness of the disease via metabolic and trophic

  9. Fibroblast Activation Protein Expression by Stromal Cells and Tumor-Associated Macrophages in Human Breast Cancer

    Science.gov (United States)

    Julia, Tchou; Zhang Paul, J; Yingtao, Bi; Celine, Satija; Rajrupa, Marjumdar; Stephen, TL; Lo, A; Haiying, Chen; Carolyn, Mies; June, Carl H; Jose, Conejo-Garcia; Ellen, Puré

    2013-01-01

    Summary Fibroblast activation protein (FAP) has long been known to be expressed in the stroma of breast cancer. However, very little is known if the magnitude of FAP expression within the stroma may have prognostic value and reflect the heterogeneous biology of the tumor cell. An earlier study had suggested that stromal FAP expression in breast cancer was inversely proportional to prognosis. We, therefore, hypothesized that stromal FAP expression may correlate with clinicopathologic variables and may serve as an adjunct prognostic factor in breast cancer. We evaluated the expression of FAP in a panel of breast cancer tissues (n=52) using a combination of immunostain analyses at the tissue and single cell level using freshly frozen or freshly digested human breast tumor samples respectively. Our results showed that FAP expression was abundantly expressed in the stroma across all breast cancer subtypes without significant correlation with clinicopathologic factors. We further identified a subset of FAP positive or FAP+ stromal cells that also expressed CD45, a pan-leukocyte marker. Using freshly dissociated human breast tumor specimens (n=5), we demonstrated that some of these FAP+ CD45+ cells were CD11b+CD14+MHC-II+ indicating that they were likely tumor associated macrophages (TAMs). Although FAP+CD45+ cells have been demonstrated in the mouse tumor stroma, our results demonstrating that human breast TAMs expressed FAP was novel and suggested that existing and future FAP directed therapy may have dual therapeutic benefits targeting both stromal mesenchymal cells and immune cells such as TAMs. More work is needed to explore the role of FAP as a potential targetable molecule in breast cancer treatment. PMID:24074532

  10. Tumor-associated macrophages are involved in tumor progression in papillary renal cell carcinoma.

    Science.gov (United States)

    Behnes, Carl Ludwig; Bremmer, Felix; Hemmerlein, Bernhard; Strauss, Arne; Ströbel, Philipp; Radzun, Heinz-Joachim

    2014-02-01

    Tumor-associated macrophages (TAMs) play a key role in cancer development. Especially, the immunosuppressive M2 phenotype is associated with increased tumor growth, invasiveness and metastasis. The differentiation of macrophages to the alternative phenotype M2 is mediated, inter alia, by macrophage colony-stimulating factor (M-CSF). Papillary renal cell carcinoma (RCC) represents a rare tumor type which, based upon histological criteria, can be subdivided into two subtypes (I and II), of which type II is associated with poor prognosis. In both subtypes, typically, a dense infiltrate of macrophages is found. In the present study, the expression of CD68, CD163, M-CSF, Ki-67, and CD31 was examined in 30 type I and 30 type II papillary RCCs (n = 60). Both types of papillary RCCs contained an equally dense infiltrate of CD68-positive macrophages. Nearly all macrophages in papillary RCC type II expressed CD163, a characteristic for M2 macrophages. In type I papillary RCC, less than 30 % of macrophages expressed CD163. Furthermore, tumor cells in type II papillary RCC expressed significantly more M-CSF and showed increased (Ki-67 expression defined) proliferative activity in comparison with type I papillary RCC. In addition, the (CD31 defined) capillary density was higher in type II than in type I papillary RCC. A dense infiltrate of M2 phenotype TAM and high M-CSF expression in tumor cells are key features of type II papillary RCC. These findings might explain why the prognosis of papillary RCC type II is worse than that of type I. PMID:24327306

  11. Non-invasive in vivo imaging of tumor-associated CD133/prominin.

    Directory of Open Access Journals (Sweden)

    Chizuko Tsurumi

    Full Text Available BACKGROUND: Cancer stem cells are thought to play a pivotal role in tumor maintenance, metastasis, tumor therapy resistance and relapse. Hence, the development of methods for non-invasive in vivo detection of cancer stem cells is of great importance. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe successful in vivo detection of CD133/prominin, a cancer stem cell surface marker for a variety of tumor entities. The CD133-specific monoclonal antibody AC133.1 was used for quantitative fluorescence-based optical imaging of mouse xenograft models based on isogenic pairs of CD133 positive and negative cell lines. A first set consisted of wild-type U251 glioblastoma cells, which do not express CD133, and lentivirally transduced CD133-overexpressing U251 cells. A second set made use of HCT116 colon carcinoma cells, which uniformly express CD133 at levels comparable to primary glioblastoma stem cells, and a CD133-negative HCT116 derivative. Not surprisingly, visualization and quantification of CD133 in overexpressing U251 xenografts was successful; more importantly, however, significant differences were also found in matched HCT116 xenograft pairs, despite the lower CD133 expression levels. The binding of i.v.-injected AC133.1 antibodies to CD133 positive, but not negative, tumor cells isolated from xenografts was confirmed by flow cytometry. CONCLUSIONS/SIGNIFICANCE: Taken together, our results show that non-invasive antibody-based in vivo imaging of tumor-associated CD133 is feasible and that CD133 antibody-based tumor targeting is efficient. This should facilitate developing clinically applicable cancer stem cell imaging methods and CD133 antibody-based therapeutics.

  12. Clinical significance of tumor-associated macrophage infiltration in supraglottic laryngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jia-Ying Lin; Xiao-Yan Li; Nakashima Tadashi; Ping Dong

    2011-01-01

    Tumor-associated macrophages (TAMs) can elicit contrasting effects on tumor progression, depending on different tumor microenvironment. This study aimed to explore the correlation between TAM infiltration and clinicopathologic characteristics, metastasis, and prognosis of supraglottic laryngeal carcinoma. TAMs in intratumoral and peritumoral regions of 84 specimens of supraglottic laryngeal carcinoma tissues were detected by immunohistochemical staining with monoclonal CD68 antibody. The density of peritumoral CD68+ TAMs in recurrence cases (9/11) and in dead cases (17/23) were significantly higher than those in non-recurrence cases (33/73) and in survival cases (25/61), with significant differences (P = 0.024 and 0.007, respectively). The Kaplan-Meier survival analysis showed a significant relationship between the infiltration of both intratumoral and peritumoral CD68+ TAMs and the overall survival of patients. The 5year survival rate was significantly lower in the group with a high density of intratumoral CD68+ TAMs than in the group with a low density (39.6% vs. 82.5%, P < 0.05). Similarly, the 5-year survival rate was significantly lower in the group with a high density of peritumoral CD68+ TAMs than in the group with a low density (50.6% vs. 73.1%, P < 0.05). Cox regression analysis revealed that T classification, distant metastasis, and intratumoral or peritumoral CD68+ TAMs were independent factors for disease-free survival, whereas T classification and intratumoral CD68+ TAMs were independent factors for overall survival. The results indicate that TAM infiltration in supraglottic laryngeal caminoma can be used to predict metastasis and prognosis and is an independent factor for prognosis.

  13. Glycosylation of the major human Pneumocystis carinii surface antigen

    DEFF Research Database (Denmark)

    Lundgren, Bettina; Koch, C; Mathiesen, Lars Reinhardt;

    1993-01-01

    It has recently been shown that the major rat P. carinii surface antigen is important for initial host-organism attachment, possibly through binding to fibronectin, mannose-binding protein, or surfactant protein A. Since a carbohydrate/lectin interaction may be involved in adhesion, we undertook...

  14. Transition metals in carbohydrate chemistry

    DEFF Research Database (Denmark)

    Madsen, Robert

    1997-01-01

    This review describes the application of transition metal mediated reactions in carbohydrate synthesis. The different metal mediated transformations are divided into reaction types and illustrated by various examples on monosaccharide derivatives. Carbon-carbon bond forming reactions are further ...

  15. Carbohydrates, Sugar, and Your Child

    Science.gov (United States)

    ... are: simple carbohydrates (or simple sugars): these include fructose, glucose, and lactose, which also are found in nutritious ... look at the ingredient list for sugar, corn syrup or sweetener, dextrose, fructose, honey, or molasses, to name just a few. ...

  16. Racemic carbohydrates - fact or fiction?

    DEFF Research Database (Denmark)

    Senning, Alexander Erich Eugen

    2007-01-01

    Chemical Abstracts Service has developed unsound practices in the naming and handling of simple carbohydrates such as aldopentoses 1, aldohexoses 2, and ketohexoses 3. Typically, the common name glucose is sometimes, inappropriately, interpreted as meaning DL-glucose DL-2d. Thus, a considerable...... number of CA names and registry numbers have been created for non-existing racemic carbohydrates and linked to irrelevant references which, moreover, in many cases cannot be retrieved by the SciFinder Scholar program....

  17. Carbohydrate drugs: current status and development prospect.

    Science.gov (United States)

    Zhang, Yan; Wang, Fengshan

    2015-04-01

    In recent years, there has been a great effort devoted to the investigation of the roles of carbohydrates in various essential biological processes and the development of carbohydrates to therapeutic drugs. This review summarizes the carbohydrate drugs which have been recorded in several pharmacopoeias, marketed, and under development. A prospect of the future development of carbohydrate drugs is discussed as well.

  18. A pigmented calcifying cystic odontogenic tumor associated with compound odontoma: a case report and review of literature

    Directory of Open Access Journals (Sweden)

    Borkosky Silvia S

    2007-09-01

    Full Text Available Abstract Background Pigmented intraosseous odontogenic lesions are rare with only 47 reported cases in the English literature. Among them, pigmented calcifying cystic odontogenic tumor, formerly known as calcifying odontogenic cyst, is the most common lesion with 20 reported cases. Methods A case of pigmented calcifying cystic odontogenic tumor associated with odontoma occurring at the mandibular canine-premolar region of a young Japanese boy is presented with radiographic, and histological findings. Special staining, electron microscopic study and immunohistochemical staining were also done to characterize the pigmentation. Results The pigments in the lesion were confirmed to be melanin by Masson-Fontana staining and by transmission electron microscopy. The presence of dendritic melanocytes within the lesion was also demonstrated by S-100 immunostaining. Conclusion The present case report of pigmented calcifying cystic odontogenic tumor associated with odontoma features a comprehensive study on melanin and melanocytes, including histochemical, immunohistochemical and transmission electron microscopic findings.

  19. Malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart: a case report

    Directory of Open Access Journals (Sweden)

    Araki Nobuhito

    2010-01-01

    Full Text Available Abstract A rare case is presented of a 61-year-old man with a malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart. The primary tumor originated in the right thigh in 1982. Since then, the patient has had repeated local recurrences in spite of repeated surgical treatment and adjuvant chemotherapy. He has developed previous metastases of the lung and heart. The patient died of cardiac involvement.

  20. The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients

    OpenAIRE

    Medrek Catharina; Pontén Fredrik; Jirström Karin; Leandersson Karin

    2012-01-01

    Abstract Background Tumor associated macrophages (TAMs) are alternatively activated macrophages that enhance tumor progression by promoting tumor cell invasion, migration and angiogenesis. TAMs have an anti-inflammatory function resembling M2 macrophages. CD163 is regarded as a highly specific monocyte/macrophage marker for M2 macrophages. In this study we evaluated the specificity of using the M2 macrophage marker CD163 as a TAM marker and compared its prognostic value with the more frequent...

  1. The National Tumor Association Foundation (ANT: A 30 year old model of home palliative care

    Directory of Open Access Journals (Sweden)

    Bonazzi Valeria

    2010-06-01

    Full Text Available Abstract Background Models of palliative care delivery develop within a social, cultural, and political context. This paper describes the 30-year history of the National Tumor Association (ANT, a palliative care organization founded in the Italian province of Bologna, focusing on this model of home care for palliative cancer patients and on its evaluation. Methods Data were collected from the 1986-2008 ANT archives and documents from the Emilia-Romagna Region Health Department, Italy. Outcomes of interest were changed in: number of patients served, performance status at admission (Karnofsky Performance Status score [KPS], length of participation in the program (days of care provided, place of death (home vs. hospital/hospice, and satisfaction with care. Statistical methods included linear and quadratic regressions. A linear and a quadratic regressions were generated; the independent variable was the year, while the dependent one was the number of patients from 1986 to 2008. Two linear regressions were generated for patients died at home and in the hospital, respectively. For each regression, the R square, the unstandardized and standardized coefficients and related P-values were estimated. Results The number of patients served by ANT has increased continuously from 131 (1986 to a cumulative total of 69,336 patients (2008, at a steady rate of approximately 121 additional patients per year and with no significant gender difference. The annual number of home visits increased from 6,357 (1985 to 904,782 (2008. More ANT patients died at home than in hospice or hospital; this proportion increased from 60% (1987 to 80% (2007. The rate of growth in the number of patients dying in hospital/hospice was approximately 40 patients/year (p 40 increased. Mean days of care for patients with KPS > 40 exceeded mean days for patients with KPS Conclusions The ANT home care model of palliative care delivery has been well-received, with progressively growing numbers

  2. Carbohydrates Through Animation: Preliminary Step

    Directory of Open Access Journals (Sweden)

    J.K. Sugai

    2004-05-01

    Full Text Available Methods of education are changing, so the educational tools must change too. The developmentof the systems of information and communication gave the opportunity to bring new technology tothe learning process. Modern education needs interactive programs that may be available to theacademic community, in order to ease the learning process and sharing of the knowledge. Then,an educational software on Carbohydrates is being developed using concept maps and FLASH-MXanimations program, and approached through six modules. The introduction of Carbohydrates wasmade by the module Carbohydrates on Nature, which shows the animations gures of a teacher andstudents, visiting a farm, identifying the carbohydrates found in vegetables, animals, and microor-ganisms, integrated by links containing short texts to help understanding the structure and functionof carbohydrates. This module was presented, as pilot experiment, to teachers and students, whichdemonstrated satisfaction, and high receptivity, by using animation and interactivitys program asstrategy to biochemistrys education. The present work is part of the project Biochemistry throughanimation, which is having continuity.

  3. Interaction of sugar stabilized silver nanoparticles with the T-antigen specific lectin, jacalin from Artocarpus integrifolia

    Science.gov (United States)

    Ayaz Ahmed, Khan Behlol; Mohammed, Ansari Sulthan; Veerappan, Anbazhagan

    2015-06-01

    The advances in nanomedicine demonstrate the anticancer properties of silver nanoparticles (AgNPs) and considered as an alternative to the available chemotherapeutic agents. Owing to the preferential interaction of Artocarpus integrifolia lectin (jacalin) with Galβ1-3GalNAcα (a chemically well-defined tumor associated antigen), a study was undertaken to understand the interaction mechanism of AgNPs with jacalin in presence of specific sugar, galactose. Fluorescence spectroscopic analysis revealed that the AgNPs binding significantly quenched the intrinsic fluorescence of jacalin through a static quenching mechanism, and a non-radiative energy transfer occurred within the molecules. Association constants obtained from the interaction of different sugar-stabilized AgNPs with jacalin are in the order of 104 M-1, this is in the same range as those obtained for the interaction of lectin with carbohydrate and hydrophobic ligand. Each subunit of the tetrameric jacalin binds one AgNPs, and the stoichiometry was unaffected by the presence of the specific sugar, galactose. Hemagglutination assay shows that sugar stabilized AgNPs interacts to jacalin at a site that is different from the saccharide-binding site. Analysis of the FTIR spectra of jacalin indicates that the binding of AgNPs does not alter the secondary structure of jacalin. More importantly, AgNPs exists in nano form even after interacting with the lectin. These results suggest that the development of lectin-AgNPs conjugate would be possible for diagnosis and treatment of cancer.

  4. 糖链抗原153与人附睾分泌蛋白4在宫颈癌患者血清中的表达%Detection of serum carbohydrate antigen 153 and human epididymis pro-tein 4 in the cervical cancer patients

    Institute of Scientific and Technical Information of China (English)

    王海英; 高金珠; 吴玉珍; 吴晓杰

    2015-01-01

    Objective To analyze the expression of serum carbohydrate antigen 153(CA153) and human epididymis protein 4 (HE4) in the cervical cancer patients. Methods 72 cases of cervix neoplasms patients received from Jun 2010 to July 2013,were divided into the cervical cancer group(36 cases)and cervical benign lesions group(36 cases)according to different pathological results, 36 cases of healthy women undergoing physical examination at the same time were chosen as control group. The level of serum CA153 and HE4 of above research subjects were detected and analyzed. Results The level of serum CA153 of cervical cancer group(79.6±14.8)U/mL was higher than that of cervical benign lesions group (t=5.17, P<0.05) and control group (t=7.31, P<0.05), there was statistically significant differ-ence; the level of serum HE4 of cervical cancer grou (216.3±8.1) pmol/L was higher that of cervical benign lesions group(t=9.71,P<0.05) and control group (t=11.84, P<0.05), there was statistically significant difference; the posi-tive rate of combined detection was higher than that of single detection, there was statistically significant difference(χ2=4.527,P<0.05); The level of serum CA153 and HE4 in III/IV stage were higher than that in I/II stage, and the difference was statistically significant (P<0.05). Conclusion The level of serum CA153 and HE4 of cervical cancer patients increase significantly. The combined detection of CA153 and HE4 can improve the diagnostic sensitivity,specificity and accordance rate of cervical cancer prominently,so it has great reference value in the early diagnosis and treatment of cervical cancer.%目的:分析血清糖链抗原153(CA153)与人附睾分泌蛋白4(HE4)在宫颈癌患者血清中的表达。方法以我院2010年6月~2013年7月收治的72例宫颈癌患者作为研究对象,根据病理检查结果分为宫颈癌组(36例)、宫颈良性病变组(36例),并将同期进行体检的36例健康女性作为对照组

  5. Diagnostic value of alpha fetoprotein (AFP),α-L-fucosidase(AFU) and carbohydrate antigen 199 (CA199)combined detection in early stage orimary hepatocellular carcinoma (PHC)%AFP、AFU、CA199联合检测对早期原发性肝癌的诊断价值

    Institute of Scientific and Technical Information of China (English)

    邓爱红; 彭燕华; 周少雄; 沈永坚; 肖海萍; 何彩云; 林经良

    2015-01-01

    目的:探讨肿瘤标志物甲胎蛋白(AFP)、α-L-岩藻糖苷酶(AFU)、糖类抗原199(CA199)对早期原发性肝癌(primary carcinoma of the liver,PHC)联合检测的诊断价值。方法:选取2013年1月到2014年5月佛山市第二人民医院肝科门诊初诊患者,通过病史、症状和查体拟诊为疑似PHC患者,再采用诊断金标准将疑似患者(研究对象)确诊分为PHC(48例)和非PHC(76例),所有研究对象均检测血清AFP、AFU和CA199,检测AFP和CA199采用化学发光法,检测AFU采用全自动生化仪器法,采用循证检验医学的方法统计各诊断价值性能指标。结果:PHC组患者AFP、AFU和CA199水平较非PHC组非常显著升高(P<0.01)。单一指标AFP、AFU和CA199检测PHC的诊断灵敏度分别为74.3%、51.4%、51.4%。单一指标AFP、AFU和CA199检测PHC的诊断特异性分别为82.4%、94.1%、94.1%。3指标并联灵敏度最高,为86.4%,其漏检率为13.6%。3指标串联和AFU/CA199串联特异性最高,约为96.5%,其误诊率为3.5%。结论:3指标并联是最佳PHC筛查联合指标,AFU和CA199串联是最佳PHC确诊联合指标。%Objective:To investigate the diagnostic value of the alpha fetoprotein (AFP), α-L- fucosidase(AFU), carbohydrate antigen 199 (CA199) and their combinations in Early Stage Primary Hepatocellular Carcinoma (PHC). Methods:Selected the Hepatological outpatients at their first visit to the second people’s hospital of Foshan from January,2013 to May,2014.Suspicious PHC patients were diagnosed by medical history, symptoms and physical check,and suspicious PHC patients were classified into PHC patients(n=48) and non-PHC patients(n=76) following the diagnosed gold criteria.The concentration of AFP and CA199 was determined by Chemiluminescence method.The concentration of AFU were determined by full automatic biochemical instrument.The assessed parameters of diagnostic value were measured using the evidence-based laboratory

  6. Berberine suppresses tumorigenicity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts

    International Nuclear Information System (INIS)

    Cortidis rhizoma (Huanglian) and its major therapeutic component, berberine, have drawn extensive attention in recent years for their anti-cancer properties. Growth inhibitory effects of berberine on multiple types of human cancer cells have been reported. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine, involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation, has also been documented. In this study, we have examined the effects of berberine on tumorigenicity and growth of nasopharyngeal carcinoma (NPC) cells and their relationship to STAT3 signaling using both in vivo and in vitro models. Berberine effectively inhibited the tumorigenicity and growth of an EBV-positive NPC cell line (C666-1) in athymic nude mice. Inhibition of tumorigenic growth of NPC cells in vivo was correlated with effective inhibition of STAT3 activation in NPC cells inside the tumor xenografts grown in nude mice. In vitro, berberine inhibited both constitutive and IL-6-induced STAT3 activation in NPC cells. Inhibition of STAT3 activation by berberine induced growth inhibition and apoptotic response in NPC cells. Tumor-associated fibroblasts were found to secret IL-6 and the conditioned medium harvested from the fibroblasts also induced STAT3 activation in NPC cells. Furthermore, STAT3 activation by conditioned medium of tumor-associated fibroblasts could be blocked by berberine or antibodies against IL-6 and IL-6R. Our observation that berberine effectively inhibited activation of STAT3 induced by tumor-associated fibroblasts suggests a role of berberine in modulating the effects of tumor stroma on the growth of NPC cells. The effective inhibition of STAT3 activation in NPC cells by berberine supports its potential use in the treatment of NPC

  7. Carbohydrates of human immunodeficiency virus

    DEFF Research Database (Denmark)

    Hansen, J E

    1992-01-01

    Elucidation of the mechanism by which viral infection induces the appearance of carbohydrate neoantigens is highly important. Results from such studies could be expected to be significant for a general understanding of the regulation of glycosylation, and perhaps especially important for the unde...

  8. Carbohydrates - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Carbohydrates URL of this page: https://medlineplus.gov/languages/carbohydrates.html Other topics A-Z A B ...

  9. Carbohydrate-based immune adjuvants

    Science.gov (United States)

    Petrovsky, Nikolai; Cooper, Peter D

    2011-01-01

    The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage. PMID:21506649

  10. The Waardenburg Syndrome Type 4 Gene, SOX10, Is a Novel Tumor-associated Antigen Identified in a Patient with a Dramatic Response to Immunotherapy

    OpenAIRE

    Khong, Hung T.; Rosenberg, Steven A.

    2002-01-01

    In this study, we have identified, for the first time, the presence of de novo cellular immune reactivity against the transcription factor SOX10, using tumor-infiltrating lymphocytes obtained from a patient who experienced a dramatic clinical response to immunotherapy. SOX10 acts as a critical transactivator of tyrosinase-related protein-2 during melanoblast development and a potent transactivator of micropthalmia-associated transcription factor, which is considered to be a master gene that c...

  11. Genetically modified natural killer cells specifically recognizing the tumor-associated antigens ErbB2/HER2 and EpCAM

    OpenAIRE

    Uherek B; Tonn T; Müller T.; Uherek C; Klingemann H-G; Wels WS

    2007-01-01

    The continuously growing natural killer (NK) cell line NK-92 is highly cytotoxic against malignant cells of various origin without affecting normal human cells. Based on this selectivity, the potential of NK-92 cells for adoptive therapy is currently being investigated in phase I clinical studies. To further enhance the antitumoral activity of NK-92 cells and expand the range of tumor entities suitable for NK-92-based therapies, here by transduction with retroviral vectors we have generated g...

  12. Histocompatibility antigen test

    Science.gov (United States)

    ... more common in certain autoimmune diseases . For example, HLA-B27 antigen is found in many people (but not ... More Ankylosing spondylitis Autoimmune disorders Bone marrow transplant HLA-B27 antigen Kidney transplant Reactive arthritis Update Date 2/ ...

  13. Species Differences in the Carbohydrate Binding Preferences of Surfactant Protein D

    DEFF Research Database (Denmark)

    Crouch, Erika C.; Smith, Kelly; McDonald, Barbara;

    2006-01-01

    Interactions of surfactant protein D (SP-D) with micro-organisms and organic antigens involve binding to the trimeric neck plus carbohydrate recognition domain (neck+CRD). In these studies, we compared the ligand binding of homologous human, rat, and mouse trimeric neck+CRD fusion proteins, each...... of the corresponding murine sequence (Asn324-Asn325) conferred a capacity to interact with immobilized maltose. Thus, ligand recognition by human SP-D involves a complex interplay between saccharide presentation, the valency of trimeric subunits, and species-specific residues that flank the primary carbohydrate...

  14. Fluorous-based carbohydrate quartz crystal microbalance.

    Science.gov (United States)

    Chen, Lei; Sun, Pengfei; Chen, Guosong

    2015-03-20

    Fluorous chemistry has brought many applications from catalysis to separation science, from supramolecular materials to analytical chemistry. However, fluorous-based quartz crystal microbalance (QCM) has not been reported so far. In the current paper, fluorous interaction has been firstly utilized in QCM, and carbohydrate-protein interaction and carbohydrate-carbohydrate interaction have been detected afterward. PMID:25541017

  15. Interactions of carbohydrates and proteins by fluorophore-assisted carbohydrate electrophoresis

    Indian Academy of Sciences (India)

    Gang-Liang Huang; Xin-Ya Mei; Peng-George Wang

    2006-06-01

    A sensitive, specific, and rapid method for the detection of carbohydrate-protein interactions is demonstrated by fluorophore-assisted carbohydrate electrophoresis (FACE). The procedure is simple and the cost is low. The advantage of this method is that carbohydrate-protein interactions can be easily displayed by FACE, and the carbohydrates do not need to be purified.

  16. Tumor-associated endothelial cells display GSTP1 and RARβ2 promoter methylation in human prostate cancer

    Directory of Open Access Journals (Sweden)

    Pohida Thomas J

    2006-03-01

    Full Text Available Abstract Background A functional blood supply is essential for tumor growth and proliferation. However, the mechanism of blood vessel recruitment to the tumor is still poorly understood. Ideally, a thorough molecular assessment of blood vessel cells would be critical in our comprehension of this process. Yet, to date, there is little known about the molecular makeup of the endothelial cells of tumor-associated blood vessels, due in part to the difficulty of isolating a pure population of endothelial cells from the heterogeneous tissue environment. Methods Here we describe the use of a recently developed technique, Expression Microdissection, to isolate endothelial cells from the tumor microenvironment. The methylation status of the dissected samples was evaluated for GSTP1 and RARβ2 promoters via the QMS-PCR method. Results Comparing GSTP1 and RARβ2 promoter methylation data, we show that 100% and 88% methylation is detected, respectively, in the tumor areas, both in epithelium and endothelium. Little to no methylation is observed in non-tumor tissue areas. Conclusion We applied an accurate microdissection technique to isolate endothelial cells from tissues, enabling DNA analysis such as promoter methylation status. The observations suggest that epigenetic alterations may play a role in determining the phenotype of tumor-associated vasculature.

  17. TLR activation of tumor-associated macrophages from ovarian cancer patients triggers cytolytic activity of NK cells.

    Science.gov (United States)

    Bellora, Francesca; Castriconi, Roberta; Dondero, Alessandra; Pessino, Anna; Nencioni, Alessio; Liggieri, Giovanni; Moretta, Lorenzo; Mantovani, Alberto; Moretta, Alessandro; Bottino, Cristina

    2014-06-01

    We analyzed the functional outcome of the interaction between tumor-associated macrophages (TAMs) and natural killer (NK) cells. TAMs from ascites of ovarian cancer patients displayed an alternatively activated functional phenotype (M2) characterized by a remarkably high frequency and surface density of membrane-bound IL-18. Upon TLR engagement, TAMs acquired a classically activated functional phenotype (M1), released immunostimulatory cytokines (IL-12, soluble IL-18), and efficiently triggered the cytolytic activity of NK cells. TAMs also induced the release of IFN-γ from NK cells, which however was significantly lower compared with that induced by in vitro-polarized M2 cells. Most tumor-associated NK cells displayed a CD56(bright) , CD16(neg) or CD56(bright) , CD16(dim) phenotype, and very poor cytolytic activities, despite an increased expression of the activation marker CD69. They also showed downregulation of DNAM-1, 2B4, and NTB-A activating receptors, and an altered chemokine receptor repertoire. Importantly however, when appropriately stimulated, NK cells from the patients, including those cells isolated from ascites, efficiently killed autologous TAMs that expressed low, "nonprotective" levels of HLA class I molecules. Overall, our data show the existence of a complex tumor microenvironment in which poorly cytolytic/immature NK cells deal with immunosuppressive tumor-educated macrophages.

  18. Butylated Hydroxyanisole Blocks the Occurrence of Tumor Associated Macrophages in Tobacco Smoke Carcinogen-Induced Lung Tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yan; Choksi, Swati; Liu, Zheng-Gang, E-mail: zgliu@helix.nih.gov [Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-04

    Tumor-associated macrophages (TAMs) promote tumorigenesis because of their proangiogenic and immune-suppressive functions. Here, we report that butylated hydroxyanisole (BHA) blocks occurrence of tumor associated macrophages (TAMs) in tobacco smoke carcinogen-induced lung tumorigenesis. Continuous administration of butylated hydroxyanisole (BHA), a ROS inhibitor, before or after NNK treatment significantly blocked tumor development, although less effectively when BHA is administered after NNK treatment. Strikingly, BHA abolished the occurrence of F4/80{sup +} macrophages with similar efficiency no matter whether it was administered before or after NNK treatment. Detection of cells from bronchioalveolar lavage fluid (BALF) confirmed that BHA markedly inhibited the accumulation of macrophages while slightly reducing the number of lymphocytes that were induced by NNK. Immunohistological staining showed that BHA specifically abolished the occurrence of CD206{sup +} TAMs when it was administered before or after NNK treatment. Western blot analysis of TAMs markers, arginase I and Ym-1, showed that BHA blocked NNK-induced TAMs accumulation. Our study clearly demonstrated that inhibiting the occurrence of TAMs by BHA contributes to the inhibition of tobacco smoke carcinogen-induced tumorigenesis, suggesting ROS inhibitors may serve as a therapeutic target for treating smoke-induced lung cancer.

  19. Cell surface carbohydrates as prognostic markers in human carcinomas

    DEFF Research Database (Denmark)

    Dabelsteen, Erik

    1996-01-01

    Tumour development is usually associated with changes in cell surface carbohydrates. These are often divided into changes related to terminal carbohydrate structures, which include incomplete synthesis and modification of normally existing carbohydrates, and changes in the carbohydrate core struc...

  20. Evidence for glycosyl-phosphatidylinositol anchoring of Toxoplasma gondii major surface antigens

    Energy Technology Data Exchange (ETDEWEB)

    Tomavo, S.; Schwarz, R.T.; Dubremetz, J.F. (Institut National de la Recheche Medicale, Villeneuve d' Ascq (France))

    1989-10-01

    The four major surface antigens of Toxoplasma gondii tachyzoites (P43, P35, P30, and P22) were made water soluble by phosphatidylinositol-specific phospholipase C (PI-PLC). These antigens were biosynthetically labeled with {sup 3}H-fatty acids, ({sup 3}H)ethanolamine, and ({sup 3}H)carbohydrates. Treatment of {sup 3}H-fatty-acid-labeled parasite lysates with PI-PLC removed the radioactive label from these antigens. A cross-reacting determinant was exposed on these antigens after PI-PLC treatment.

  1. Pattern of distribution of blood group antigens on human epidermal cells during maturation

    DEFF Research Database (Denmark)

    Dabelsteen, Erik; Buschard, Karsten; Hakomori, Sen-Itiroh

    1984-01-01

    The distribution in human epidermis of A, B, and H blood group antigens and of a precursor carbohydrate chain, N-acetyl-lactosamine, was examined using immunofluorescence staining techniques. The material included tissue from 10 blood group A, 4 blood group B, and 9 blood group O persons. Murine...... on the lower spinous cells whereas H antigen was seen predominantly on upper spinous cells or on the granular cells. Epithelia from blood group A or B persons demonstrated A or B antigens, respectively, but only if the tissue sections were trypsinized before staining. In such cases A or B antigens were found...... monoclonal antibodies were used to identify H antigen (type 2 chain) and N-acetyl-lactosamine. Human antisera were used to identify A and B antigens. In all groups N-acetyl-lactosamine and H antigen were found on the cell membranes of the spinous cell layer. N-acetyl-lactosamine was present mainly...

  2. Bacterial surface antigen-specific monoclonal antibodies used to detect beer spoilage pediococci.

    Science.gov (United States)

    Whiting, M S; Ingledew, W M; Lee, S Y; Ziola, B

    1999-08-01

    Fourteen monoclonal antibodies (Mabs) were isolated that react with surface antigens of Pediococcus beer spoilage organisms, including P. damnosus, P. pentosaceous, P. acidilactici, and unspeciated isolates. Immunoblotting, enzyme immunoassays (EIAs) of protease- and neuraminidase-treated surface antigen extracts, carbohydrate competition EIAs, and cardiolipin EIAs were used to characterize the bacterial antigens involved in Mab binding. Antigen stability in situ was tested by protease treatment or surface antigen extraction of washed bacteria. In most cases, the Mabs bind to Pediococcus surface antigens that appear to be covalently bound cell wall polymers resistant to alteration or removal from the bacterial surface. These bacterial surface antigen reactive Mabs show good potential for rapid, sensitive, and specific immunoassay detection of Pediococcus beer spoilage organisms.

  3. ABO blood group antigens in oral mucosa. What is new?

    DEFF Research Database (Denmark)

    Dabelsteen, Erik

    2002-01-01

    which represent secondary gene products. They are synthesized in a stepwise fashion from a precursor by the action of different glycosyltransferases. In non-keratinized oral mucosa, a sequential elongation of the carbohydrates is associated with differentiation of epithelial cells, resulting...... in expression of precursors on basal cells and A/B antigens on spinous cells. Reduction or complete deletion of A/B antigen expression in oral carcinomas has been reported, a phenotypic change that is correlated with invasive and metastatic potential of the tumours and with the mortality rates of the patients....... Disappearance of the antigens is ascribed to the absence of A or B transferase gene expression. Several studies have shown that loss of A and B antigen expression is associated with increased cell motility, invasion in matrigel, and tumourigenecity in syngenic animals. In vivo studies of human oral wound...

  4. Carbohydrate Microarrays in Plant Science

    DEFF Research Database (Denmark)

    Fangel, Jonatan Ulrik; Pedersen, H.L.; Vidal-Melgosa, S.;

    2012-01-01

    Almost all plant cells are surrounded by glycan-rich cell walls, which form much of the plant body and collectively are the largest source of biomass on earth. Plants use polysaccharides for support, defense, signaling, cell adhesion, and as energy storage, and many plant glycans are also important...... industrially and nutritionally. Understanding the biological roles of plant glycans and the effective exploitation of their useful properties requires a detailed understanding of their structures, occurrence, and molecular interactions. Microarray technology has revolutionized the massively high...... for plant research and can be used to map glycan populations across large numbers of samples to screen antibodies, carbohydrate binding proteins, and carbohydrate binding modules and to investigate enzyme activities....

  5. Expression of uPAR in tumor-associated stromal cells is associated with colorectal cancer patient prognosis: a TMA study

    International Nuclear Information System (INIS)

    The receptor for urokinase-type plasminogen activator (uPAR) is associated with cancer development and progression. Within the tumor microenvironment uPAR is expressed by malignant cells as well as tumor-associated stromal cells. However, the contribution of uPAR expression in these stromal cells to malignancy and patient survival in colorectal cancer is still unclear. This study compares the association of uPAR expression in both colorectal tumor-associated stromal cells and neoplastic cells with clinico-pathological characteristics and patient survival using tissue micro arrays (TMA). Immunohistochemical staining of uPAR expression was performed on tumor tissue from 262 colorectal cancer patients. Kaplan-Meier, log rank, and uni- and multivariate Cox’s regression analyses were used to calculate associations between uPAR expression and patient survival. In the colorectal tumor-associated stromal microenvironment, uPAR is expressed in macrophages, (neoangiogenic) endothelial cells and myofibroblasts. uPAR expression in tumor-associated stromal cells and neoplastic cells (and both combined) were negatively associated with overall survival (OS) and Disease Free Survival (DFS). Uni- and multivariate Cox’s regression analysis for combined uPAR expression in tumor-associated stromal and neoplastic cells showed significant and independent negative associations with OS and DFS. Only uPAR expression in tumor-associated stromal cells showed independent significance in the uni- and multivariate analysis for DFS. This study demonstrates a significant independent negative association between colorectal cancer patient survival and uPAR expression in especially tumor-associated stromal cells

  6. Molecular Cloning, Carbohydrate Specificity and the Crystal Structure of Two Sclerotium rolfsii Lectin Variants

    Directory of Open Access Journals (Sweden)

    Vassiliki I. Peppa

    2015-06-01

    Full Text Available SRL is a cell wall associated developmental-stage specific lectin secreted by Sclerotium rolfsii, a soil-born pathogenic fungus. SRL displays specificity for TF antigen (Galβ1→3GalNAc-α-Ser//Thr expressed in all cancer types and has tumour suppressing effects in vivo. Considering the immense potential of SRL in cancer research, we have generated two variant gene constructs of SRL and expressed in E. coli to refine the sugar specificity and solubility by altering the surface charge. SSR1 and SSR2 are two different recombinant variants of SRL, both of which recognize TF antigen but only SSR1 binds to Tn antigen (GalNAcα-Ser/Thr. The glycan array analysis of the variants demonstrated that SSR1 recognizes TF antigen and their derivative with high affinity similar to SRL but showed highest affinity towards the sialylated Tn antigen, unlike SRL. The carbohydrate binding property of SSR2 remains unaltered compared to SRL. The crystal structures of the two variants were determined in free form and in complex with N-acetylglucosamine at 1.7 Å and 1.6 Å resolution, respectively. Structural analysis highlighted the structural basis of the fine carbohydrate specificity of the two SRL variants and results are in agreement with glycan array analysis.

  7. Molecular Cloning, Carbohydrate Specificity and the Crystal Structure of Two Sclerotium rolfsii Lectin Variants.

    Science.gov (United States)

    Peppa, Vassiliki I; Venkat, Hemalatha; Kantsadi, Anastassia L; Inamdar, Shashikala R; Bhat, Ganapati G; Eligar, Sachin; Shivanand, Anupama; Chachadi, Vishwanath B; Satisha, Gonchigar J; Swamy, Bale M; Skamnaki, Vassiliki T; Zographos, Spyridon E; Leonidas, Demetres D

    2015-01-01

    SRL is a cell wall associated developmental-stage specific lectin secreted by Sclerotium rolfsii, a soil-born pathogenic fungus. SRL displays specificity for TF antigen (Galβ1→3GalNAc-α-Ser//Thr) expressed in all cancer types and has tumour suppressing effects in vivo. Considering the immense potential of SRL in cancer research, we have generated two variant gene constructs of SRL and expressed in E. coli to refine the sugar specificity and solubility by altering the surface charge. SSR1 and SSR2 are two different recombinant variants of SRL, both of which recognize TF antigen but only SSR1 binds to Tn antigen (GalNAcα-Ser/Thr). The glycan array analysis of the variants demonstrated that SSR1 recognizes TF antigen and their derivative with high affinity similar to SRL but showed highest affinity towards the sialylated Tn antigen, unlike SRL. The carbohydrate binding property of SSR2 remains unaltered compared to SRL. The crystal structures of the two variants were determined in free form and in complex with N-acetylglucosamine at 1.7 Å and 1.6 Å resolution, respectively. Structural analysis highlighted the structural basis of the fine carbohydrate specificity of the two SRL variants and results are in agreement with glycan array analysis. PMID:26076107

  8. Bioengineering T cells to target carbohydrate to treat opportunistic fungal infection

    OpenAIRE

    Kumaresan, Pappanaicken R.; Manuri, Pallavi R.; Albert, Nathaniel D.; Maiti, Sourindra; Singh, Harjeet; Mi, Tiejuan; Roszik, Jason; Rabinovich, Brian; Olivares, Simon; Krishnamurthy, Janani; Zhang, Ling; Najjar, Amer M.; Huls, M. Helen; Lee, Dean A.; Champlin, Richard E.

    2014-01-01

    Patients with compromised T-cell function are at risk for opportunistic fungal infections. We have developed a novel approach to restore immunity by using a fungal pattern-recognition receptor Dectin-1 to redirect T-cell specificity to carbohydrate antigen in the fungal cell wall. We did so by genetically modifying T cells using the nonviral Sleeping Beauty gene-transfer system to enforce expression of a chimeric antigen receptor (CAR) that recapitulates the specificity of Dectin-1 (D-CAR). T...

  9. Antigen-Specific Cytotoxic T Lymphocytes can Target Chemoresistant Side-Population Tumor Cells in Hodgkin’s Lymphoma

    OpenAIRE

    Shafer, Jessica A.; Cruz, Conrad R.; Leen, Ann M; Ku, Stephanie; LU, AN; Rousseau, Alexandra; Heslop, Helen E.; Rooney, Cliona M; Bollard, Catherine M.; Foster, Aaron E.

    2010-01-01

    Side-population (SP) analysis has been used to identify progenitor cells from normal and malignant tissues as well as revealing tumor cells with increased resistance to radiation and chemotherapy. Despite enhanced chemoresistance, tumor SP cells may still express tumor associated antigens (TAA) which may render them susceptible to elimination by the immune system. In this study, we show that both Hodgkin’s lymphoma (HL) cell lines and primary HL tumor samples contain a distinct SP phenotype. ...

  10. Antitumor Activity of Liposomal Prednisolone Phosphate Depends on the Presence of Functional Tumor-Associated Macrophages in Tumor Tissue

    Directory of Open Access Journals (Sweden)

    Manuela Banciu

    2008-02-01

    Full Text Available Prednisolone phosphate (PLP encapsulated in long-circulating liposomes (LCLs (LCL-PLP exerts antitumor activity through the inhibition of tumor angiogenesis. It is known that tumor-associated macrophages (TAMs play a crucial role in tumor growth as they are actively involved in promoting and maintaining tumor angiogenesis. To gain more insight into the antiangiogenic mechanisms of LCL-PLP, this study aimed to investigate the role of TAM in the antitumor mode of action of LCL-PLP in B16.F10 melanoma-bearing mice. Our results show that TAMs have a pivotal function in the growth of B16.F10 melanoma through the production of pro-angiogenic/pro-inflammatory factors. One of the major inhibitory actions of LCL-PLP on tumor growth is the reduction of the TAM-mediated production of pro-angiogenic factors, whereas production of anti-angiogenic factors by these cells is hardly affected.

  11. Novel sulfonamide bearing coumarin scaffolds as selective inhibitors of tumor associated carbonic anhydrase isoforms IX and XII.

    Science.gov (United States)

    Chandak, Navneet; Ceruso, Mariangela; Supuran, Claudiu T; Sharma, Pawan K

    2016-07-01

    Four novel scaffolds consisting of total 24 compounds (1a-1o, 2a-2c, 3a-3c and 4a-4c) bearing aromatic sulfonamide and coumarin moieties connected through various linkers were synthesized in order to synergize the inhibition potential of both the moieties against four selected human carbonic anhydrase isoforms (hCA I, II, IX & XII). All compounds were found to be potent inhibitors of tumor associated hCA IX & XII while at the same time required large amounts to inhibit off-targeted housekeeping hCA I & II. Selectivity was more pronounced against hCA II over I, and hCA XII over IX. Results were compared with antitumor drug acetazolamide. One derivative 2b of series 2 was found to be a better selective inhibitor of hCA IX and XII. PMID:27137360

  12. A systematic study of chemogenomics of carbohydrates.

    Science.gov (United States)

    Gu, Jiangyong; Luo, Fang; Chen, Lirong; Yuan, Gu; Xu, Xiaojie

    2014-03-01

    Chemogenomics focuses on the interactions between biologically active molecules and protein targets for drug discovery. Carbohydrates are the most abundant compounds in natural products. Compared with other drugs, the carbohydrate drugs show weaker side effects. Searching for multi-target carbohydrate drugs can be regarded as a solution to improve therapeutic efficacy and safety. In this work, we collected 60 344 carbohydrates from the Universal Natural Products Database (UNPD) and explored the chemical space of carbohydrates by principal component analysis. We found that there is a large quantity of potential lead compounds among carbohydrates. Then we explored the potential of carbohydrates in drug discovery by using a network-based multi-target computational approach. All carbohydrates were docked to 2389 target proteins. The most potential carbohydrates for drug discovery and their indications were predicted based on a docking score-weighted prediction model. We also explored the interactions between carbohydrates and target proteins to find the pathological networks, potential drug candidates and new indications.

  13. Tumor-associated macrophages%肿瘤相关巨噬细胞研究进展

    Institute of Scientific and Technical Information of China (English)

    吴琼; 姜祎群; 孙建方

    2015-01-01

    肿瘤相关巨噬细胞是肿瘤相关慢性炎症中的关键细胞,促进肿瘤生长、增殖、血管生成、侵袭、转移及化疗抵抗.巨噬细胞根据环境不同大致可极化为经典活化型巨噬细胞(M1型)及替代活化型巨噬细胞(M2型).环氧酶2、核因子κB、Toll样受体信号途径、缺氧、原癌基因MYC、Notch信号通路及细胞因子等参与肿瘤相关巨噬细胞发生M1-M2型别转化.巨噬细胞的表型及功能随着肿瘤进展的不同阶段而变化,针对巨噬细胞的抗肿瘤药物治疗,应取决于肿瘤所处的阶段.%Tumor-associated macrophages (TAMs) are key cells in tumor-associated chronic inflammation,and can promote tumor growth,proliferation,angiogenesis,invasion,metastasis and chemotherapy resistance.Under different circumstances,macrophages can be polarized into classically activated macrophages (M1) and alternatively activated macrophages (M2).Cyclooxygenase 2,nuclear factorκB,Toll like receptor (TLR) signaling pathway,anoxia,the protooncogene MYC,Notch signaling pathway and cytokines are all involved in the transition of TAMs from M1 to M2 phenotype.The phenotype and function of TAMs vary with tumor progression,so antitumor drug therapies targeting macrophages should depend on the stage of tumors.

  14. Targeting tumor-associated immune suppression with selective protein kinase A type I (PKAI) inhibitors may enhance cancer immunotherapy.

    Science.gov (United States)

    Hussain, Muzammal; Shah, Zahir; Abbas, Nasir; Javeed, Aqeel; Mukhtar, Muhammad Mahmood; Zhang, Jiancun

    2016-01-01

    Despite the tremendous progress in last few years, the cancer immunotherapy has not yet improved disease-free because of the tumor-associated immune suppression being a major barrier. Novel trends to enhance cancer immunotherapy aims at harnessing the therapeutic manipulation of signaling pathways mediating the tumor-associated immune suppression, with the general aims of: (a) reversing the tumor immune suppression; (b) enhancing the innate and adaptive components of anti-tumor immunosurveillance, and (c) protecting immune cells from the suppressive effects of T regulatory cells (Tregs) and the tumor-derived immunoinhibitory mediators. A particular striking example in this context is the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A type I (PKAI) pathway. Oncogenic cAMP/PKAI signaling has long been implicated in the initiation and progression of several human cancers. Emerging data indicate that cAMP/PKAI signaling also contributes to tumor- and Tregs-derived suppression of innate and adaptive arms of anti-tumor immunosurveillance. Therapeutically, selective PKAI inhibitors have been developed which have shown promising anti-cancer activity in pre-clinical and clinical settings. Rp-8-Br-cAMPS is a selective PKAI antagonist that is widely used as a biochemical tool in signal transduction research. Collateral data indicate that Rp-8-Br-cAMPS has shown immune-rescuing potential in terms of enhancing the innate and adaptive anti-tumor immunity, as well as protecting adaptive T cells from the suppressive effects of Tregs. Therefore, this proposal specifically implicates that combining selective PKAI antagonists/inhibitors with cancer immunotherapy may have multifaceted benefits, such as rescuing the endogenous anti-tumor immunity, enhancing the efficacy of cancer immunotherapy, and direct anti-cancer effects.

  15. Carbohydrates

    Science.gov (United States)

    ... with added sugar provide calories, but they lack vitamins, minerals, and fiber. Because they lack nutrients, these foods ... foods. In addition to calories, whole foods provide vitamins, minerals, and fiber. By making smart food choices, you ...

  16. Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma.

    Science.gov (United States)

    Hegde, Meenakshi; Corder, Amanda; Chow, Kevin K H; Mukherjee, Malini; Ashoori, Aidin; Kew, Yvonne; Zhang, Yi Jonathan; Baskin, David S; Merchant, Fatima A; Brawley, Vita S; Byrd, Tiara T; Krebs, Simone; Wu, Meng Fen; Liu, Hao; Heslop, Helen E; Gottschalk, Stephen; Gottachalk, Stephen; Yvon, Eric; Ahmed, Nabil

    2013-11-01

    Preclinical and early clinical studies have demonstrated that chimeric antigen receptor (CAR)-redirected T cells are highly promising in cancer therapy. We observed that targeting HER2 in a glioblastoma (GBM) cell line results in the emergence of HER2-null tumor cells that maintain the expression of nontargeted tumor-associated antigens. Combinational targeting of these tumor-associated antigens could therefore offset this escape mechanism. We studied the single-cell coexpression patterns of HER2, IL-13Rα2, and EphA2 in primary GBM samples using multicolor flow cytometry and immunofluorescence, and applied a binomial routine to the permutations of antigen expression and the related odds of complete tumor elimination. This mathematical model demonstrated that cotargeting HER2 and IL-13Rα2 could maximally expand the therapeutic reach of the T cell product in all primary tumors studied. Targeting a third antigen did not predict an added advantage in the tumor cohort studied. We therefore generated bispecific T cell products from healthy donors and from GBM patients by pooling T cells individually expressing HER2 and IL-13Rα2-specific CARs and by making individual T cells to coexpress both molecules. Both HER2/IL-13Rα2-bispecific T cell products offset antigen escape, producing enhanced effector activity in vitro immunoassays (against autologous glioma cells in the case of GBM patient products) and in an orthotopic xenogeneic murine model. Further, T cells coexpressing HER2 and IL-13Rα2-CARs exhibited accentuated yet antigen-dependent downstream signaling and a particularly enhanced antitumor activity.

  17. Role of carbohydrate in determining the immunochemical properties of the hemagglutinin of influenza A virus

    Energy Technology Data Exchange (ETDEWEB)

    Gitelman, A.K.; Berezin, V.A.; Kharitonenkov, I.G. (Akademiya Meditsinskikh Nauk SSSR, Moscow)

    1981-01-01

    Most of the carbohydrate was removed from influenza with MRC II (H3N2) and its purified hemagglutinin (HA) on treatment with glycosidases, including ..cap alpha..-mannosidase, ..beta..-N-acetylglucosaminidase, ..beta..-galactosidase and ..cap alpha..-fucosidase. The release of 50 per cent of the carbohydrate from intact virus particles significantly affected hemagglutinating activity. The ability of untreated and glycosidase-treated virus to inhibit the binding of antibodies directed against the hemagglutinin was almost indistinguishable by competitive radioimmunoassay (RIA). Up to 60 per cent of the carbohydrate from the purified HA of influenza virus could be removed. The antigenicity of glycosidase treated HA molecules decreased 8-fold compared to intact HAs as measured by competitive RIA. In addition, glycosidase digestion of /sup 125/I-labeled HA resulted in a decrease in its reactivity in direct RIA. We conclude that the carbohydrate portion of the HA of influenza virus is not of major importance in defining the antigenicity of HA.

  18. Quantitative RT-PCR assays for the determination of urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 mRNA in primary tumor tissue of breast cancer patients: comparison to antigen quantification by ELISA.

    NARCIS (Netherlands)

    Biermann, J.C.; Holzscheiter, L.; Kotzsch, M.; Luther, T.; Kiechle-Bahat, M.; Sweep, F.C.; Span, P.N.; Schmitt, M.; Magdolen, V.

    2008-01-01

    Urokinase-type plasminogen activator (uPA) and its inhibitor plasminogen activator inhibitor type 1 (PAI-1) play a key role in tumor-associated processes such as the degradation of extracellular matrix proteins, tissue remodeling, cell adhesion, migration, and invasion. High antigen levels of uPA an

  19. Variability in expression of cell surface antigens of Candida albicans during morphogenesis.

    OpenAIRE

    Brawner, D L; Cutler, J. E.

    1986-01-01

    The location and expression of two different cell surface antigens on germinating and nongerminating Candida albicans cells was examined by using transmission electron microscopy after labeling with monoclonal antibodies (H9 or C6) and immunocolloidal gold. Immunodeterminant expression of the two carbohydrate antigens was followed from early germination events through 20 h of development. The determinant detected by H9 antibody, which was initially lost from the mother cell surface and prefer...

  20. Precocious puberty secondary to a mixed germ cell-sex cord-stromal tumor associated with an ovarian yolk sac tumor: a case report

    OpenAIRE

    Metwalley Kotb; Elsers Dalia; Farghaly Hekma; Abdel-Lateif Hanaa; Abdel-Kader Mohamed

    2012-01-01

    Abstract Introduction Ovarian tumors are the least common cause of sexual precocity in girls. Mixed germ cell-sex cord-stromal tumors associated with a yolk sac tumor of the ovary are rare neoplasms, of which only a small number of well-documented cases have been described so far. Here, we report precocious puberty in a four-year-old Egyptian girl caused by a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary. Case presentation A four-year-old Egyptian girl w...

  1. Carbohydrate metabolism in Spirochaeta stenostrepta.

    Science.gov (United States)

    Hespell, R B; Canale-Parola, E

    1970-07-01

    The pathways of carbohydrate metabolism in Spirochaeta stenostrepta, a free-living, strictly anaerobic spirochete, were studied. The organism fermented glucose to ethyl alcohol, acetate, lactate, CO(2), and H(2). Assays of enzymatic activities in cell extracts, and determinations of radioactivity distribution in products formed from (14)C-labeled glucose indicated that S. stenostrepta degraded glucose via the Embden-Meyerhof pathway. The spirochete utilized a clostridial-type clastic reaction to metabolize pyruvate to acetyl-coenzyme A, CO(2), and H(2), without production of formate. Acetyl-coenzyme A was converted to ethyl alcohol by nicotinamide adenine dinucleotide-dependent acetaldehyde and alcohol dehydrogenase activities. Phosphotransacetylase and acetate kinase catalyzed the formation of acetate from acetyl-coenzyme A. Hydrogenase and lactate dehydrogenase activities were detected in cell extracts. A rubredoxin was isolated from cell extracts of S. stenostrepta. Preparations of this rubredoxin stimulated acetyl phosphate formation from pyruvate by diethylaminoethyl cellulose-treated extracts of S. stenostrepta, an indication that rubredoxin may participate in pyruvate cleavage by this spirochete. Nutritional studies showed that S. stenostrepta fermented a variety of carbohydrates, but did not ferment amino acids or other organic acids. An unidentified growth factor present in yeast extract was required by the organism. Exogenous supplements of biotin, riboflavin, and vitamin B(12) were either stimulatory or required for growth. PMID:5423371

  2. The effects of carbohydrate variation in isocaloric diets on glycogenolysis and gluconeogenesis in healthy men

    NARCIS (Netherlands)

    Bisschop, PH; Arias, AMP; Ackermans, MT; Endert, E; Pijl, H; Kuipers, F; Meijer, AJ; Sauerwein, HP; Romijn, JA

    2000-01-01

    To evaluate the effect of dietary carbohydrate content on postabsorptive glucose metabolism, we quantified gluconeogenesis and glycogenolysis after 11 days of high carbohydrate (85% carbohydrate), control (44% carbohydrate), and very low carbohydrate (2% carbohydrate) diets in six healthy men. Diets

  3. Recent advance in carbohydrate-based cancer vaccines%肿瘤糖疫苗的研究进展

    Institute of Scientific and Technical Information of China (English)

    霍常鑫; 叶新山

    2012-01-01

    The abnormal glycans expressing on the surface of tumor cells are good targets to develop carbohydrate-based anti-cancer vaccines. However, one of the major problems is that carbohydrate antigens possess weak immunogenicity. This review summarizes the recent efforts to overcome this problem: glycoconjugates produced by coupling the carbohydrate antigens and proper carrier proteins improve their immunogenicity, many glycoconjugates have entered clinical trials; the vaccines become chemically well-defined when coupling the carbohydrate antigens with a T-cell peptide epitope and an immunostimulant to form fully synthetic multi-component glycoconjugate vaccines; the modification of carbohydrate antigens in combination with the technology of metabolic oligosaccharide engineering of tumor cells induces a strong immune response; and the fact that the antibodies elicited against the unnatural carbohydrate antigens can recognize the native carbohydrate antigens on tumor cells provides a new promising strategy for the development of anti-cancer vaccines.%肿瘤细胞表面异常表达的糖抗原为肿瘤糖疫苗的研究提供了合适的靶标,然而由于这些糖抗原的免疫原性较差,这又给糖疫苗的发展带来了很大的困难.本文概述了近年来科学工作者在提高肿瘤糖疫苗的免疫原性方面所做的努力:半合成的肿瘤糖疫苗将糖抗原与蛋白共价连接,已经有很多疫苗进入了临床试验;随后发展的全合成的肿瘤糖疫苗将糖抗原、T细胞表位和内源性佐剂共价连接,使疫苗的结构和组成更加确定;基于细胞代谢糖工程的肿瘤糖疫苗将非天然的糖疫苗与细胞表面代谢糖工程相结合,得到了强烈的免疫应答;某些基于天然糖抗原结构修饰的疫苗产生的抗体也可以与天然糖抗原发生交叉反应,这为肿瘤糖疫苗的发展提供了新的方向.

  4. Suicide Gene Therapy to Increase the Safety of Chimeric Antigen Receptor-Redirected T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Monica Casucci, Attilio Bondanza

    2011-01-01

    Full Text Available Chimeric antigen receptors (CARs are generated by fusing the antigen-binding motif of a monoclonal antibody (mAb with the signal transduction machinery of the T-cell receptor (TCR. The genetic modification of T lymphocytes with chimeric receptors specific for tumor-associated antigens (TAAs allows for the redirection towards tumor cells. Clinical experience with CAR-redirected T cells suggests that antitumor efficacy associates with some degree of toxicity, especially when TAA expression is shared with healthy tissues. This situation closely resembles the case of allogeneic hematopoietic stem cell transplantation (HSCT, wherein allorecognition causes both the graft-versus-leukemia (GVL effect and graft-versus-host disease (GVHD. Suicide gene therapy, i.e. the genetic induction of a conditional suicide phenotype into donor T cells, enables dissociating the GVL effect from GVHD. Applying suicide gene modification to CAR-redirected T cells may therefore greatly increase their safety profile and facilitate their clinical development.

  5. Sperm protein 17 is an oncofetal antigen: a lesson from a murine model.

    Science.gov (United States)

    Arnaboldi, F; Menon, A; Menegola, E; Di Renzo, F; Mirandola, L; Grizzi, F; Figueroa, J A; Cobos, E; Jenkins, M; Barajon, I; Chiriva-Internati, Maurizio

    2014-10-01

    Sperm protein 17 (Sp17) was originally identified in the flagellum of spermatozoa and subsequently included in the subfamily of tumor-associated antigens known as cancer-testes antigens (CTA). Sp17 has been associated with the motility and migratory capacity in tumor cells, representing a link between gene expression patterns in germinal and tumor cells of different histological origins. Here we review the relevance of Sp17 expression in the mouse embryo and cancerous tissues, and present additional data demonstrating Sp17 complex expression pattern in this murine model. The expression of Sp17 in embryonic as well as adult neoplastic cells, but not normal tissues, suggests this protein should be considered an "oncofetal antigen." Further investigations are necessary to elucidate the mechanisms and functional significance of Sp17 aberrant expression in human adult cells and its implication in the pathobiology of cancer. PMID:24811209

  6. Biochemical software: Carbohydrates on Laboratory

    Directory of Open Access Journals (Sweden)

    D.N. Heidrich

    2005-07-01

    Full Text Available Educators around  the  world  are  being  challenged  to  develop  and  design  better and  more  effective strategies for student learning  using a variety  of modern  resources.  In this  present  work, an educa- tional  hypermedia  software  was constructed as a support tool to biochemistry teaching.  Occurrence, structure, main  characteristics and  biological  function  of the  biomolecule  Carbohydrates were pre- sented  through  modules.  The  software was developed  using concept  maps,  ISIS-Draw,  and  FLASH- MX animation program.  The chapter  Carbohydrates on Laboratory illustrates experimental methods of carbohydrates characterization, through  animation of a laboratory scenery.   The  subject was de- veloped showing reactions  as Bial, Benedict, Selliwanoff, Barfoed, Phenol  Sulphuric,  and Iodines, and also enzymatic  reactions  as glucose oxidase and amylase.  There are also links with short texts  in order to help the understanding of the contents  and principles of laboratory practice  as well as background reactions. Application of the software to undergraduate students and high school teachers  showed an excellent  acceptance.   All of them  considered  the  software  a very good learning  tool.  Both  teachers and students welcomed this program  as it is more flexible, and allows the learning in a more individual rhythm. In addition, application of the software would be suitable  to a more effective learning  and it is less expensive than conventional experimental teaching.

  7. Carbohydrate clearance receptors in transfusion medicine

    DEFF Research Database (Denmark)

    Sørensen, Anne Louise Tølbøll; Clausen, Henrik; Wandall, Hans H

    2012-01-01

    Complex carbohydrates play important functions for circulation of proteins and cells. They provide protective shields and refraction from non-specific interactions with negative charges from sialic acids to enhance circulatory half-life. For recombinant protein therapeutics carbohydrates are espe...

  8. Conversion of carbohydrates to levulinic acid esters

    DEFF Research Database (Denmark)

    2014-01-01

    The present invention relates to the field of converting carbohydrates into levulinic acid, a platform chemical for many chemical end products. More specifically the invention relates to a method for converting carbohydrates such as mono-, di- or polysaccharides, obtained from for example biomass...

  9. Derivatization Reaction of Carbohydrates with Urea as the Reagent and Fluorimetric Determination of Carbohydrates

    Institute of Scientific and Technical Information of China (English)

    YANG,Jing-He(杨景和); CAO,Xi-Hui(曹西慧); WANG,Min(王敏); WU,Xia(吴霞); SUN,Chang-Xia(孙长侠)

    2002-01-01

    It is found that in the presence of sulfuric acid carbohydrates condense with urea to afford the condensation products, which emit fluorescence. Under optimum conditions, the fluorescence intensities of system are proportional to the concentrations of carbohydrates. Based on this linear relationship,quantitative determination of kinds of carbohydrates has been made. Among an the carbohydrates tested, the sensitivity of α-rhamnose is the highest and its limits of detection reaches 3.5 × 10-8 mol/L. So α-rhamnose can be selectively determed in the presence of other carbohydrates. A interaction mechanism is also discussed.

  10. Prognostic value of lymphocyte/monocyte ratio in advanced Hodgkin lymphoma: correlation with International Prognostic Score and tumor associated macrophages.

    Science.gov (United States)

    Jakovic, Ljubomir R; Mihaljevic, Biljana S; Andjelic, Bosko M; Bogdanovic, Andrija D; Perunicic Jovanovic, Maja D; Babic, Dragan D; Bumbasirevic, Vladimir Z

    2016-08-01

    We studied the prognostic significance of the absolute lymphocyte/monocyte count ratio (ALC/AMC), its contribution to the prognostic value of the International Prognostic Score (IPS), and evaluated if ALC/AMC could serve as a proxy for the frequency of CD68 + tumor-associated macrophages (TAMs) in 101 patients with advanced Hodgkin lymphoma (HL). The receiver operating characteristic (ROC) curve identified best cut-off values of 2.0 for ALC/AMC and 25% for CD68 + TAM. Patients with ALC/AMC  2 and > 25% CD68 + TAM had an inferior overall survival (OS) and event-free survival (EFS). Spearman's test also uncovered a significant correlation between the ALC/AMC and TAM. Multivariate analysis identified ALC/AMC  2 and > 25% CD68 + TAM as poor prognostic factors of OS and EFS. After evaluating ALC/AMC and IPS, we stratified patients into three progressively-worse-outcome groups (low-risk: 0 risk factors; intermediate: 1 risk factor; high: 2 risk factors). Our study encourages the combination of ALC/AMC with IPS, for refining risk prediction in advanced HL patients. PMID:26727349

  11. Infiltration of M2 Tumor-Associated Macrophages in Oral Squamous Cell Carcinoma Correlates with Tumor Malignancy

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Kazumasa [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Hiroi, Miki [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Shimada, Jun [Division of Oral and Maxillofacial Surgery, Department of Diagnosis and Therapeutics, Meikai University of School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan); Ohmori, Yoshihiro, E-mail: ohmori@dent.meikai.ac.jp [Division of Microbiology and Immunology, Department of Oral Biology and Tissue Engineering, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283 (Japan)

    2011-09-28

    Tumor-associated macrophages (TAMs) are a major cellular component in the tumor microenvironment of many solid tumors. The functional competence of TAMs varies depending on the type of tumors and their respective microenvironments. The classically activated M1 macrophages exhibit antitumor functions, whereas the alternatively activated M2 macrophages exhibit protumor functions that contribute to tumor development and progression. Although TAMs have been detected in oral squamous cell carcinoma (OSCC), little is known about their phenotype. In the present study, we performed an immunohistochemical analysis to identify TAMs in surgically resected specimens from 50 patients with OSCC and evaluated the relationship between infiltrated TAMs and the pathological grade of OSCC. Positive staining for CD163, which has been used as a marker for M2 macrophages, was observed in OSCC specimens, and the percentages of CD163{sup +} cells were significantly increased based on the pathological grade. CD163{sup +} cells were detected in the tumor stroma in grade I tumors, whereas an increase in the CD163{sup +} cells in the tumor nest was observed in higher grades of tumors. Although infiltrated CD4{sup +} and CD8{sup +} T cells were detected in all pathological grades of OSCC, no correlation between the infiltrated T cells and the CD163{sup +} TAMs was observed. These results indicate that the infiltrated TAMs in OSCC have an M2 phenotype and that the M2 macrophages may participate in the development of OSCC.

  12. ROS play a critical role in the differentiation of alternatively activated macrophages and the occurrence of tumor-associated macrophages

    Institute of Scientific and Technical Information of China (English)

    Yan Zhang; Swati Choksi; Kun Chen; Yelena Pobezinskaya; Ilona Linnoila; Zheng-Gang Liu

    2013-01-01

    Differentiation to different types of macrophages determines their distinct functions.Tumor-associated macrophages (TAMs) promote tumorigenesis owing to their proangiogenic and immune-suppressive functions similar to those of alternatively activated (M2) macrophages.We report that reactive oxygen species (ROS) production is critical for macrophage differentiation and that inhibition of superoxide (O2-) production specifically blocks the differentiation of M2 macrophages.We found that when monocytes are triggered to differentiate,O2-is generated and is needed for the biphasic ERK activation,which is critical for macrophage differentiation.We demonstrated that ROS elimination by butylated hydroxyanisole (BHA) and other ROS inhibitors blocks macrophage differentiation.However,the inhibitory effect of ROS elimination on macrophage differentiation is overcome when cells are polarized to classically activated (M1),but not M2,macrophages.More importantly,the continuous administration of the ROS inhibitor BHA efficiently blocked the occurrence of TAMs and markedly suppressed tumorigenesis in mouse cancer models.Targeting TAMs by blocking ROS can be a potentially effective method for cancer treatment.

  13. Co-evolution of tumor-associated macrophages and tumor neo-vessels during cervical cancer invasion

    Science.gov (United States)

    Jiang, Shuting; Yang, Yuehong; Fang, Min; Li, Xianglang; Yuan, Xiuxue; Yuan, Jingping

    2016-01-01

    Considering the crucial significance of the tumor microenvironment in cancer development and progression, the present study aimed to investigate the changes in macrophages and angiogenesis during the cervical cancer (CC) progression process from chronic cervicitis to cervical intraepithelial neoplasia grades I–III (CIN I–III) to CC. This investigation included quantitative analysis and assessment of the spatial associations between tumor-associated macrophages (TAMs) and tumor neo-vessels. The conventional immunohistochemistry staining technique was used to detect cluster of differentiation (CD)68 and CD105 biomarker expression for TAMs and tumor neo-vessels, respectively. In addition, with the assistance of quantum dot (QD)-based two-component in situ imaging technology, the expression of the TAMs and tumor neo-vessels could be observed simultaneously. The quantitative analysis and co-evolution of the TAMs and tumor neo-vessels could then be processed. During the progression process from chronic cervicitis to cervical CIN I–III, and ultimately to invasive CC, the expression of the macrophages and neo-vessels in the tumor microenvironment increased synchronously. According to the quantitative analysis results, the median value of the TAM density was higher in the CC group (5,540.14) than in the CIN I–III group (2,502.17) and the chronic cervicitis group (1,403.31), with statistical significance in all three groups (Pbiology of cancer invasion. PMID:27698836

  14. CD163+ Tumor-Associated Macrophages Correlated with Poor Prognosis and Cancer Stem Cells in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Ke-Fei He

    2014-01-01

    Full Text Available Tumor-associated macrophages (TAMs play an important role in the progression and prognostication of numerous cancers. However, the role and clinical significance of TAM markers in oral squamous cell carcinoma (OSCC has not been elucidated. The present study was designed to investigate the correlation between the expression of TAM markers and pathological features in OSCC by tissue microarray. Tissue microarrays containing 16 normal oral mucosa, 6 oral epithelial dysplasia, and 43 OSCC specimens were studied by immunohistochemistry. We observed that the protein expression of the TAM markers CD68 and CD163 as well as the cancer stem cell (CSC markers ALDH1, CD44, and SOX2 increased successively from the normal oral mucosa to OSCC. The expressions of CD68 and CD163 were significantly associated with lymph node status, and SOX2 was significantly correlated with pathological grade and lymph node status, whereas ALDH1 was correlated with tumor stage. Furthermore, CD68 was significantly correlated with CD163, SOX2, and ALDH1 (P<0.05. Kaplan-Meier analysis revealed that OSCC patients overexpressing CD163 had significantly worse overall survival (P<0.05. TAM markers are associated with cancer stem cell marker and OSCC overall survival, suggesting their potential prognostic value in OSCC.

  15. A think tank of TINK/TANKs: tumor-infiltrating/tumor-associated natural killer cells in tumor progression and angiogenesis.

    Science.gov (United States)

    Bruno, Antonino; Ferlazzo, Guido; Albini, Adriana; Noonan, Douglas M

    2014-08-01

    Tumor-infiltrating leukocytes are often induced by the cancer microenvironment to display a protumor, proangiogenic phenotype. This "polarization" has been described for several myeloid cells, in particular macrophages. Natural killer (NK) cells represent another population of innate immune cells able to infiltrate tumors. The role of NK in tumor progression and angiogenesis has not yet been fully investigated. Several studies have shown that tumor-infiltrating NK (here referred to as "TINKs") and tumor-associated NK (altered peripheral NK cells, which here we call "TANKs") are compromised in their ability to lysew tumor cells. Recent data have suggested that they are potentially protumorigenic and can also acquire a proangiogenic phenotype. Here we review the properties of TINKs and TANKs and compare their activities to that of NK cells endowed with a physiological proangiogenic phenotype, in particular decidual NK cells. We speculate on the potential origins of TINKs and TANKs and on the immune signals involved in their differentiation and polarization. The TINK and TANK phenotype has broad implications in the immune response to tumors, ranging from a deficient control of cancer and cancer stem cells to an altered crosstalk with other relevant players of the immune response, such as dendritic cells, to induction of cancer angiogenesis. With this recently acquired knowledge that has not yet been put into perspective, we point out new potential avenues for therapeutic intervention involving NK cells as a target or an ally in oncology. PMID:25178695

  16. A think tank of TINK/TANKs: tumor-infiltrating/tumor-associated natural killer cells in tumor progression and angiogenesis.

    Science.gov (United States)

    Bruno, Antonino; Ferlazzo, Guido; Albini, Adriana; Noonan, Douglas M

    2014-08-01

    Tumor-infiltrating leukocytes are often induced by the cancer microenvironment to display a protumor, proangiogenic phenotype. This "polarization" has been described for several myeloid cells, in particular macrophages. Natural killer (NK) cells represent another population of innate immune cells able to infiltrate tumors. The role of NK in tumor progression and angiogenesis has not yet been fully investigated. Several studies have shown that tumor-infiltrating NK (here referred to as "TINKs") and tumor-associated NK (altered peripheral NK cells, which here we call "TANKs") are compromised in their ability to lysew tumor cells. Recent data have suggested that they are potentially protumorigenic and can also acquire a proangiogenic phenotype. Here we review the properties of TINKs and TANKs and compare their activities to that of NK cells endowed with a physiological proangiogenic phenotype, in particular decidual NK cells. We speculate on the potential origins of TINKs and TANKs and on the immune signals involved in their differentiation and polarization. The TINK and TANK phenotype has broad implications in the immune response to tumors, ranging from a deficient control of cancer and cancer stem cells to an altered crosstalk with other relevant players of the immune response, such as dendritic cells, to induction of cancer angiogenesis. With this recently acquired knowledge that has not yet been put into perspective, we point out new potential avenues for therapeutic intervention involving NK cells as a target or an ally in oncology.

  17. An adenovirus vector incorporating carbohydrate binding domains utilizes glycans for gene transfer.

    Directory of Open Access Journals (Sweden)

    Julius W Kim

    Full Text Available BACKGROUND: Vectors based on human adenovirus serotype 5 (HAdV-5 continue to show promise as delivery vehicles for cancer gene therapy. Nevertheless, it has become clear that therapeutic benefit is directly linked to tumor-specific vector localization, highlighting the need for tumor-targeted gene delivery. Aberrant glycosylation of cell surface glycoproteins and glycolipids is a central feature of malignant transformation, and tumor-associated glycoforms are recognized as cancer biomarkers. On this basis, we hypothesized that cancer-specific cell-surface glycans could be the basis of a novel paradigm in HAdV-5-based vector targeting. METHODOLOGY/PRINCIPAL FINDINGS: As a first step toward this goal, we constructed a novel HAdV-5 vector encoding a unique chimeric fiber protein that contains the tandem carbohydrate binding domains of the fiber protein of the NADC-1 strain of porcine adenovirus type 4 (PAdV-4. This glycan-targeted vector displays augmented CAR-independent gene transfer in cells with low CAR expression. Further, we show that gene transfer is markedly decreased in cells with genetic glycosylation defects and by inhibitors of glycosylation in normal cells. CONCLUSIONS/SIGNIFICANCE: These data provide the initial proof-of-concept for HAdV-5 vector-mediated gene delivery based on the presence of cell-surface carbohydrates. Further development of this new targeting paradigm could provide targeted gene delivery based on vector recognition of disease-specific glycan biomarkers.

  18. Unique carbohydrate-carbohydrate interactions are required for high affinity binding between FcgammaRIII and antibodies lacking core fucose.

    Science.gov (United States)

    Ferrara, Claudia; Grau, Sandra; Jäger, Christiane; Sondermann, Peter; Brünker, Peter; Waldhauer, Inja; Hennig, Michael; Ruf, Armin; Rufer, Arne Christian; Stihle, Martine; Umaña, Pablo; Benz, Jörg

    2011-08-01

    Antibody-mediated cellular cytotoxicity (ADCC), a key immune effector mechanism, relies on the binding of antigen-antibody complexes to Fcγ receptors expressed on immune cells. Antibodies lacking core fucosylation show a large increase in affinity for FcγRIIIa leading to an improved receptor-mediated effector function. Although afucosylated IgGs exist naturally, a next generation of recombinant therapeutic, glycoenginereed antibodies is currently being developed to exploit this finding. In this study, the crystal structures of a glycosylated Fcγ receptor complexed with either afucosylated or fucosylated Fc were determined allowing a detailed, molecular understanding of the regulatory role of Fc-oligosaccharide core fucosylation in improving ADCC. The structures reveal a unique type of interface consisting of carbohydrate-carbohydrate interactions between glycans of the receptor and the afucosylated Fc. In contrast, in the complex structure with fucosylated Fc, these contacts are weakened or nonexistent, explaining the decreased affinity for the receptor. These findings allow us to understand the higher efficacy of therapeutic antibodies lacking the core fucose and also suggest a unique mechanism by which the immune system can regulate antibody-mediated effector functions.

  19. Technological aspects of functional food-related carbohydrates.

    NARCIS (Netherlands)

    Voragen, A.G.J.

    1998-01-01

    Carbohydrates in food occur as natural constituents or are added as ingredients or additives. The most important endogenous carbohydrates in food are starch, depolymerized starch, sucrose, lactose, glucose, fructose and sorbitol (digestible) and carbohydrates such as raffinose, stachyose, resistant

  20. Determination of serum β-human chorionic gonadotropin, progesterone, carbohydrate antigen 125,creatinekinase and creatinekinase/progesterone for early diagnosis of ectopic pregnancy%血清人绒毛膜促性腺激素β亚基、孕酮、糖类抗原125、肌酸激酶及肌酸激酶/孕酮值在异位妊娠早期诊断中的应用价值

    Institute of Scientific and Technical Information of China (English)

    刘金花; 徐吟亚; 姜波玲

    2011-01-01

    Objective To explore the value of serum p-human chorionic gonadotropin (p-HCG), progesterone( P), carbohydrate antigen 125 (CA125) ,creatinekinase(CK) and creatinekinase/progesterone (CK/P) for early diagnosis of ec-topic pregnancy (EP). Methods Serum contents of p-HCG,P,CA125 (with chemiluminescent immunoassay) and CK (with enzymatic kinetic method) were determined in 72 patients with suspected early ectopic pregnancy (observation group) and 72 normal pregnant women (control group) as to analyze the value of serum p-HCG combined with P,CA125,CK and CK/P for early diagnosis of EP. Results The serum levels of p-HCG, P,CA125 in the observation group were significantly lower than those in the control group (P 0. 05) ; the serum level of CK/P in the observation group was significantly higher than that in the control group (P<0.01).The specificity and accuracy of serum p-HCG combined with P,CA125,CK/P for early diagnosis of EP were respectively 88.9% and 91.7%. Conclusion Combined determination of p-HCG,P.CA125 and CK/P may contribute to the early diagnosis of EP and help to provide a valuable clinical diagnosis.%目的 探讨血清人绒毛膜促性腺激素β亚基(β-HCG)、孕酮(P)、糖类抗原125 (CA125)、肌酸激酶(CK)及CK/P值在异位妊娠早期诊断中的应用价值.方法 选择临床可疑异位妊娠患者72例作为观察组,正常宫内妊娠72例作为对照组.于治疗前采用化学发光免疫分析法测定血清β-HCG、P及CA125水平,采用酶动力学方法检测CK水平,在血清β-HCG基础上分析多项指标联合检测对早期异位妊娠的诊断价值.结果 观察组血清β-HCG、P及CA125水平均显著低于对照组(P<0.01);观察组的CK较对照组略有升高,但差别无统计学意义(P>0.05);观察组的血清CK/P值显著高于对照组(P<0.01).血清β-HCG、P、CA125及CK/P值4项指标联合检测可将诊断特异度、准确性分别提高至88.9%、91.7%.结论 血清β-HCG、P、CA125及CK/P值

  1. Tissue expression of the tumour associated antigen CA242 in benign and malignant pancreatic lesions. A comparison with CA 50 and CA 19-9.

    OpenAIRE

    Haglund, C.; Lindgren, J.; Roberts, P. J.; Kuusela, P.; Nordling, S.

    1989-01-01

    The expression of a novel tumour associated antigen CA 242, defined by the monoclonal antibody C 242, was studied by immunoperoxidase staining in formalin-fixed, paraffin-embedded tissue sections from normal pancreata, pancreata with pancreatitis and benign and malignant pancreatic neoplasms. The antigenic determinant of the C 242 antibody is a sialylated carbohydrate structure, related but chemically different from tumour marker antigens CA 19-9 and CA 50. Thirty-eight of 41 (93%) well to mo...

  2. Antigen-specific T cell activation independently of the MHC: chimeric antigen receptor (CAR-redirected T cells.

    Directory of Open Access Journals (Sweden)

    Hinrich eAbken

    2013-11-01

    Full Text Available Adoptive T cell therapy has recently shown powerful in initiating a lasting anti-tumor response with spectacular therapeutic success in some cases. Specific T cell therapy, however, is limited since a number of cancer cells are not recognized by T cells due to various mechanisms including the limited availability of tumor-specific T cells and deficiencies in antigen processing or major histocompatibility complex (MHC expression of cancer cells. To make adoptive cell therapy applicable for the broad variety of cancer entities, patient's T cells are engineered ex vivo with pre-defined specificity by a recombinant chimeric antigen receptor (CAR which consists in the extracellular part of an antibody-derived domain for binding with a tumor-associated antigen and in the intracellular part of a TCR-derived signaling moiety for T cell activation. The specificity of CAR mediated T cell recognition is defined by the antibody domain, is independent of MHC presentation and can be extended to any target for which an antibody is available. We discuss the advantages and limitations of MHC-independent T cell targeting by an engineered CAR and review most significant progress recently made in early stage clinical trials to treat cancer.

  3. Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Kun Shang

    Full Text Available Ulcerative colitis (UC is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC. However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM, followed by repeated dextran sulfate sodium (DSS ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP-9 and neutrophil elastase (NE, accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer.

  4. Specific Inhibition of the VEGFR-3 Tyrosine Kinase by SAR131675 Reduces Peripheral and Tumor Associated Immunosuppressive Myeloid Cells

    Directory of Open Access Journals (Sweden)

    Nicolas Espagnolle

    2014-02-01

    Full Text Available Myeloid derived suppressor cells (MDSCs and tumor-associated macrophages (TAMs represent prominent components in cancer progression. We previously showed that inhibition of the VEGFR-3 pathway by SAR131675 leads to reduction of TAM infiltration and tumor growth. Here, we found that treatment with SAR131675 prevents the accumulation of immunosuppressive blood and splenic MDSCs which express VEGFR-3, in 4T1 tumor bearing mice. Moreover we showed that soluble factors secreted by tumor cells promote MDSCs proliferation and differentiation into M2 polarized F4/80+ macrophages. In addition, cell sorting and transcriptomic analysis of tumor infiltrating myeloid cells revealed the presence of a heterogeneous population that could be divided into 3 subpopulations: (i immature cells with a MDSC phenotype (GR1+/CD11b+/F4/80−; (ii “immuno-incompetent” macrophages (F4/80high/CD86neg/MHCIILow strongly expressing M2 markers such as Legumain, CD206 and Mgl1/2 and (iii “immuno-competent”-M1 like macrophages (F4/80Low/CD86+/MHCIIHigh. SAR131675 treatment reduced MDSCs in lymphoid organs as well as F4/80High populations in tumors. Interestingly, in the tumor SAR131675 was able to increase the immunocompetent M1 like population (F4/80low. Altogether these results demonstrate that the specific VEGFR-3 inhibitor SAR131675 exerts its anti tumoral activity by acting on different players that orchestrate immunosuppression and cancer progression in a tumoral context: MDSCs in peripheral lymphoid organs and TAMs infiltrating the tumor.

  5. Tumor-associated macrophages in glioblastoma multiforme-a suitable target for somatostatin receptor-based imaging and therapy?

    Directory of Open Access Journals (Sweden)

    Constantin Lapa

    Full Text Available Glioblastoma multiforme (GBM is the most common primary brain tumor in adults. Tumor-associated macrophages (TAM have been shown to promote malignant growth and to correlate with poor prognosis. [1,4,7,10-tetraazacyclododecane-NN',N″,N'″-tetraacetic acid]-d-Phe1,Tyr3-octreotate (DOTATATE labeled with Gallium-68 selectively binds to somatostatin receptor 2A (SSTR2A which is specifically expressed and up-regulated in activated macrophages. On the other hand, the role of SSTR2A expression on the cell surface of glioma cells has not been fully elucidated yet. The aim of this study was to non-invasively assess SSTR2A expression of both glioma cells as well as macrophages in GBM.15 samples of patient-derived GBM were stained immunohistochemically for macrophage infiltration (CD68, proliferative activity (Ki67 as well as expression of SSTR2A. Anti-CD45 staining was performed to distinguish between resident microglia and tumor-infiltrating macrophages. In a subcohort, positron emission tomography (PET imaging using 68Ga-DOTATATE was performed and the semiquantitatively evaluated tracer uptake was compared to the results of immunohistochemistry.The amount of microglia/macrophages ranged from 50% in the tumor samples with the vast majority being resident microglial cells. A strong SSTR2A immunostaining was observed in endothelial cells of proliferating vessels, in neurons and neuropile. Only faint immunostaining was identified on isolated microglial and tumor cells. Somatostatin receptor imaging revealed areas of increased tracer accumulation in every patient. However, retention of the tracer did not correlate with immunohistochemical staining patterns.SSTR2A seems not to be overexpressed in GBM samples tested, neither on the cell surface of resident microglia or infiltrating macrophages, nor on the surface of tumor cells. These data suggest that somatostatin receptor directed imaging and treatment strategies are less promising in GBM.

  6. Tumor-associated macrophages%肿瘤相关巨噬细胞研究进展

    Institute of Scientific and Technical Information of China (English)

    李彬; 朱迅

    2010-01-01

    单核巨噬细胞是一种多功能细胞,对不同的微环境信号应答表现出不同的功能.而极化的M1和M2巨噬细胞是巨噬细胞功能表现的两个极端.其中侵润到肿瘤组织的巨噬细胞受肿瘤诱导产生的细胞因子的影响使巨噬细胞表现出巨噬细胞M2型表型,这些极化的巨噬细胞在破坏适应性免疫反应和促进肿瘤生长与进展方面具有重要作用.肿瘤相关巨噬细胞(TAM)可以促进肿瘤进展包括促进肿瘤生长、侵润、转移,促进血管生长和免疫抑制等,因而研究TAM具有重要意义.%Mononuclear phagocytes are versatile cells that can express different functional programs in response to microenvironmental signals. Fully polarized Ml and M2 macrophages are the extremes of a continuum of functional states. Macrophages that infiltrate tumor tissues are driven by tumor-derived cytokines to acquire a polarized M2 phenotype. These functionally polarized cells play a key role in subversion of adaptive immunity and in inflammatory circuits that promote tumor growth and progression. It is notable that tumor-associated macrophages promote the proliferation, invasiveness and metastasis of tumor cells ,and participate in neovas-cularization, and immunosuppression of the tumor.

  7. Specific Inhibition of the VEGFR-3 Tyrosine Kinase by SAR131675 Reduces Peripheral and Tumor Associated Immunosuppressive Myeloid Cells

    Energy Technology Data Exchange (ETDEWEB)

    Espagnolle, Nicolas [UMR5273 INSERM U1031/CNRS/EFS StromaLab, Toulouse 31432 (France); Barron, Pauline; Mandron, Marie; Blanc, Isabelle; Bonnin, Jacques [Sanofi Recherche et Développement, Early to Candidate DPU, Toulouse 31036 (France); Agnel, Magali; Kerbelec, Erwan [Molecular Biology Unit, Biologics Department, Sanofi, Vitry-sur-Seine 94400 (France); Herault, Jean Pascal; Savi, Pierre; Bono, Françoise; Alam, Antoine, E-mail: antoine.alam@sanofi.com [Sanofi Recherche et Développement, Early to Candidate DPU, Toulouse 31036 (France)

    2014-02-28

    Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) represent prominent components in cancer progression. We previously showed that inhibition of the VEGFR-3 pathway by SAR131675 leads to reduction of TAM infiltration and tumor growth. Here, we found that treatment with SAR131675 prevents the accumulation of immunosuppressive blood and splenic MDSCs which express VEGFR-3, in 4T1 tumor bearing mice. Moreover we showed that soluble factors secreted by tumor cells promote MDSCs proliferation and differentiation into M2 polarized F4/80+ macrophages. In addition, cell sorting and transcriptomic analysis of tumor infiltrating myeloid cells revealed the presence of a heterogeneous population that could be divided into 3 subpopulations: (i) immature cells with a MDSC phenotype (GR1+/CD11b+/F4/80{sup −}); (ii) “immuno-incompetent” macrophages (F4/80{sup high}/CD86{sup neg}/MHCII{sup Low}) strongly expressing M2 markers such as Legumain, CD206 and Mgl1/2 and (iii) “immuno-competent”-M1 like macrophages (F4/80{sup Low}/CD86{sup +}/MHCII{sup High}). SAR131675 treatment reduced MDSCs in lymphoid organs as well as F4/80{sup High} populations in tumors. Interestingly, in the tumor SAR131675 was able to increase the immunocompetent M1 like population (F4/80{sup low}). Altogether these results demonstrate that the specific VEGFR-3 inhibitor SAR131675 exerts its anti tumoral activity by acting on different players that orchestrate immunosuppression and cancer progression in a tumoral context: MDSCs in peripheral lymphoid organs and TAMs infiltrating the tumor.

  8. Development of Y-shaped peptide for constructing nanoparticle systems targeting tumor-associated macrophages in vitro and in vivo

    Science.gov (United States)

    Yan, Lu; Gao, Yunxiang; Pierce, Ryan; Dai, Liming; Kim, Julian; Zhang, Mei

    2014-04-01

    Tumor-associated macrophage (TAM) is increasingly being viewed as a target of great interest in tumor microenvironment due to its important role in the progression and metastasis of cancers. It has been shown that TAM indeed overexpresses unique surface marker legumain. In this study, we designed and synthesized a Y-shaped legumain-targeting peptide (Y-Leg) with functional groups allowing for further conjugation with imaging and therapeutic moieties (vide infra). The in vitro cell experiments using FITC-conjugated Y-Leg revealed its specific and selective interaction with M2-polarized macrophages (i.e., TAMs) with preference to M1 macrophages, and that the interaction was not interfered with by conjugating FITC to its functional group. Further, we constructed a nanotube system by grafting Y-Leg onto oxidized carbon nanotubes (OCNTs) loaded with paramagnetic Fe3O4 nanoparticles. The intravenous injection of the resultant Y-Leg-OCNT/Fe3O4 nanotubes to 4T1 mammary tumor-bearing mouse led to the magnetic resonance imaging (MRI) of TAM-infiltrated tumor microenvironment, revealing the targeting specificity of Y-Leg-conjugated nanotubes in vivo. The Y shape of peptide and its functional groups containing amines and imidazole can protonate at different pHs, contributing to the in vitro and in vivo targeting specificity. This study represents the first development of novel peptide and peptide-grafted nanotube system targeting M2-polarized TAMs in vivo. The methodology developed in this study is applicable to the construction of various multifunctional nanoparticle systems for selectively targeting, imaging and manipulating of TAMs for the diagnosis and treatment of cancers and inflammatory diseases identified with macrophage-infiltrated disease tissue.

  9. Utilization of carbohydrates by radiation processing

    Energy Technology Data Exchange (ETDEWEB)

    Kume, T. E-mail: kume@taka.jaeri.go.jp; Nagasawa, N.; Yoshii, F

    2002-03-01

    Upgrading and utilization of carbohydrates such as chitosan, sodium alginate, carrageenan, cellulose, pectin have been investigated for recycling these bio-resources and reducing the environmental pollution. These carbohydrates were easily degraded by irradiation and various kinds of biological activities such as anti-microbial activity, promotion of plant growth, suppression of heavy metal stress, phytoalexins induction, etc. were induced. On the other hand, some carbohydrate derivatives, carboxymethylcellulose and carboxymethylstarch, could be crosslinked under certain radiation condition and produce the biodegradable hydrogel for medical and agricultural use.

  10. Molecular simulations of carbohydrate-protein complexes

    OpenAIRE

    Eid, Sameh Mansour Abbas

    2013-01-01

    I. Generation and validation of a free-energy model for carbohydrate binding. Carbohy-drates play a key role in a variety of physiological and pathological processes and, hence, represent a rich source for the development of novel therapeutic agents. Being able to predict binding mode and binding affinity is an essential, yet lacking, aspect of the stru-cture-based design of carbohydrate-based ligands. To this end, we assembled a diverse data set of 316 carbohydrate–protein crystal structu...

  11. Tumor vasoproliferativo associado à tuberculose ocular presumida: relato de caso Vasoproliferative tumor associated with presumed ocular tuberculosis: case report

    Directory of Open Access Journals (Sweden)

    Luciana Duarte Rodrigues

    2007-06-01

    hipofluorescência por bloqueio (proliferação do EPR. Os tumores vasoproliferativos secundários são proliferações gliovasculares da retina e estão associados a várias condições oculares que afetam a retina e a coróide. Devido ao grande número de complicações associadas aos tumores vasoproliferativos da retina, com perda visual significativa, estes devem ser tratados no momento do diagnóstico. O tratamento de escolha para estes tumores é a crioterapia. A triancinolona intravítrea, por seus efeitos antiangiogênicos, pode ser utilizada como tratamento adjuvante. Até o presente momento, a associação de tumor vasoproliferativo e tuberculose ocular não foi relatada na literatura. O tratamento do tumor vasoproliferativo secundário com crioterapia e injeção intravítrea da triancionolona surge como nova opção terapêutica. Mais estudos são necessários para comprovar a eficácia deste tratamento.PURPOSE: To describe a case of vasoproliferative tumor associated with presumed ocular tuberculosis treated with cryotherapy and intravitreal triamcinolone injection. STUDY DESIGN/PATIENT AND METHODS: Interventional case report. A 42-year-old female patient reported inflammation of the right eye 1 year ago, treated with oral prednisone for 30 days. She referred blurred vision in the right eye since childhood. Ophthalmologic examination showed 20/400 visual acuity in the right eye. Biomicroscopy and intraocular pressure were normal. Fundus examination showed vascularized elevated lesion, associated with serous retinal detachment and hard exudates at the inferior periphery. The lesion was surrounded by extensive area of hyperplastic retinal pigment epithelium. The macula showed attenuation of the foveal reflex. Ocular ultrasound showed a 2.25 mm height vascularized lesion. Serologic examination, hemogram and thorax RX were normal. PPD was considered strong reactor and tuberculosis was diagnosed after positive BK research. Considering the clinical aspects, the ocular

  12. Carbohydrate feeding and exercise: effect of beverage carbohydrate content.

    Science.gov (United States)

    Murray, R; Seifert, J G; Eddy, D E; Paul, G L; Halaby, G A

    1989-01-01

    The purpose of this study was to determine the effect of ingesting fluids of varying carbohydrate content upon sensory response, physiologic function, and exercise performance during 1.25 h of intermittent cycling in a warm environment (Tdb = 33.4 degrees C). Twelve subjects (7 male, 5 female) completed four separate exercise sessions; each session consisted of three 20 min bouts of cycling at 65% VO2max, with each bout followed by 5 min rest. A timed cycling task (1200 pedal revolutions) completed each exercise session. Immediately prior to the first 20 min cycling bout and during each rest period, subjects consumed 2.5 ml.kg BW-1 of water placebo (WP), or solutions of 6%, 8%, or 10% sucrose with electrolytes (20 mmol.l-1 Na+, 3.2 mmol.l-1 K+). Beverages were administered in double blind, counterbalanced order. Mean (+/- SE) times for the 1200 cycling task differed significantly: WP = 13.62 +/- 0.33 min, *6% = 13.03 +/- 0.24 min, 8% = 13.30 +/- 0.25 min, 10% = 13.57 +/- 0.22 min (* = different from WP and 10%, P less than 0.05). Compared to WP, ingestion of the CHO beverages resulted in higher plasma glucose and insulin concentrations, and higher RER values during the final 20 min of exercise (P less than 0.05). Markers of physiologic function and sensory perception changed similarly throughout exercise; no differences were observed among subjects in response to beverage treatments for changes in plasma concentrations of lactate, sodium, potassium, for changes in plasma volume, plasma osmolality, rectal temperature, heart rate, oxygen uptake, rating of perceived exertion, or for indices of gastrointestinal distress, perceived thirst, and overall beverage acceptance.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Structural basis for the carbohydrate recognition of the Sclerotium rolfsii lectin.

    Science.gov (United States)

    Leonidas, Demetres D; Swamy, Bale M; Hatzopoulos, George N; Gonchigar, Sathisha J; Chachadi, Vishwanath B; Inamdar, Shashikala R; Zographos, Spyros E; Oikonomakos, Nikos G

    2007-05-11

    The crystal structure of a novel fungal lectin from Sclerotium rolfsii (SRL) in its free form and in complex with N-acetyl-d-galactosamine (GalNAc) and N-acetyl- d -glucosamine (GlcNAc) has been determined at 1.1 A, 2.0 A, and 1.7 A resolution, respectively. The protein structure is composed of two beta-sheets, which consist of four and six beta-strands, connected by two alpha-helices. Sequence and structural comparisons reveal that SRL is the third member of a newly identified family of fungal lectins, which includes lectins from Agaricus bisporus and Xerocomus chrysenteron that share a high degree of structural similarity and carbohydrate specificity. The data for the free SRL are the highest resolution data for any protein of this family. The crystal structures of the SRL in complex with two carbohydrates, GalNAc and GlcNAc, which differ only in the configuration of a single epimeric hydroxyl group, provide the structural basis for its carbohydrate specificity. SRL has two distinct carbohydrate-binding sites, a primary and a secondary. GalNAc binds at the primary site, whereas GlcNAc binds only at the secondary site. Thus, SRL has the ability to recognize and probably bind at the same time two different carbohydrate structures. Structural comparison to Agaricus bisporus lectin-carbohydrate complexes reveals that the primary site is also able to bind the Thomsen-Friedenreich antigen (Galbeta1-->3GalNAc-alpha- glycan structures) whereas the secondary site cannot. The features of the molecular recognition at the two sites are described in detail. PMID:17391699

  14. Workshop to establish databases of carbohydrate spectra

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-31

    The workshop was organized to formulate guidelines for establishing spectral databases of complex carbohydrates. The databases will enable the scientific community to avoid the great waste of research effort and funds that frequently occurs when carbohydrate chemists are forced to duplicate the structural characterization of previously characterized complex carbohydrates. Chemists waste their effort on repetitive characterizations because in the absence of spectral databases they are unaware they are analyzing a known molecule until they have completely determined its structure. Chemists will be able to avoid much of this wasted effort when the collections of mass and of nuclear magnetic resonance (NMR) spectra initiated at the workshop are subsequently developed into searchable databases. Then scientists only need query the databases with the spectrum or with information defining the spectrum of an unidentified carbohydrate to find out if it has been previously characterized.

  15. The Origin of the Constant Carbohydrate Diet

    Directory of Open Access Journals (Sweden)

    Charles Herbert Read

    2009-01-01

    Full Text Available The Constant Carbohydrate diet, based entirely on carbohydrate exchanges, is now widely used in the dietary treatment of diabetes mellitus. Being based on sound scientific principles and simple in design, the Constant Carabohydrate diet is appropriate for all those having diabetes mellitus, young or old, no matter their ethncity. This report describes why and how it was developed in 1951. Its simplicity makes it adaptable to all ethnic diets.

  16. The Origin of the Constant Carbohydrate Diet

    Directory of Open Access Journals (Sweden)

    Read CharlesHerbert

    2008-01-01

    Full Text Available The Constant Carbohydrate diet, based entirely on carbohydrate exchanges, is now widely used in the dietary treatment of diabetes mellitus. Being based on sound scientific principles and simple in design, the Constant Carabohydrate diet is appropriate for all those having diabetes mellitus, young or old, no matter their ethncity. This report describes why and how it was developed in 1951. Its simplicity makes it adaptable to all ethnic diets.

  17. Pollutant effects on genotoxic parameters and tumor-associated protein levels in adults: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Baeyens Willy

    2008-06-01

    Full Text Available Abstract Background This study intended to investigate whether residence in areas polluted by heavy industry, waste incineration, a high density of traffic and housing or intensive use of pesticides, could contribute to the high incidence of cancer observed in Flanders. Methods Subjects were 1583 residents aged 50–65 from 9 areas with different types of pollution. Cadmium, lead, p,p'-DDE, hexachlorobenzene, PCBs and dioxin-like activity (Calux test were measured in blood, and cadmium, t,t'-muconic acid and 1-hydroxypyrene in urine. Effect biomarkers were prostate specific antigen, carcinoembryonic antigen and p53 protein serum levels, number of micronuclei per 1000 binucleated peripheral blood cells, DNA damage (comet assay in peripheral blood cells and 8-hydroxy-deoxyguanosine in urine. Confounding factors were taken into account. Results Overall significant differences between areas were found for carcinoembryonic antigen, micronuclei, 8-hydroxy-deoxyguanosine and DNA damage. Compared to a rural area with mainly fruit production, effect biomarkers were often significantly elevated around waste incinerators, in the cities of Antwerp and Ghent, in industrial areas and also in other rural areas. Within an industrial area DNA strand break levels were almost three times higher close to industrial installations than 5 kilometres upwind of the main industrial installations (p Conclusion Levels of internal exposure, and residence near waste incinerators, in cities, or close to important industries, but not in areas with intensive use of pesticides, showed positive correlations with biomarkers associated with carcinogenesis and thus probably contribute to risk of cancer. In some rural areas, the levels of these biomarkers were not lower than in the rest of Flanders.

  18. Dietary Carbohydrates and Childhood Functional Abdominal Pain.

    Science.gov (United States)

    Chumpitazi, Bruno P; Shulman, Robert J

    2016-01-01

    Childhood functional gastrointestinal disorders (FGIDs) affect a large number of children throughout the world. Carbohydrates (which provide the majority of calories consumed in the Western diet) have been implicated both as culprits for the etiology of symptoms and as potential therapeutic agents (e.g., fiber) in childhood FGIDs. In this review, we detail how carbohydrate malabsorption may cause gastrointestinal symptoms (e.g., bloating) via the physiologic effects of both increased osmotic activity and increased gas production from bacterial fermentation. Several factors may play a role, including: (1) the amount of carbohydrate ingested; (2) whether ingestion is accompanied by a meal or other food; (3) the rate of gastric emptying (how quickly the meal enters the small intestine); (4) small intestinal transit time (the time it takes for a meal to enter the large intestine after first entering the small intestine); (5) whether the meal contains bacteria with enzymes capable of breaking down the carbohydrate; (6) colonic bacterial adaptation to one's diet, and (7) host factors such as the presence or absence of visceral hypersensitivity. By detailing controlled and uncontrolled trials, we describe how there is a general lack of strong evidence supporting restriction of individual carbohydrates (e.g., lactose, fructose) for childhood FGIDs. We review emerging evidence suggesting that a more comprehensive restriction of fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) may be effective. Finally, we review how soluble fiber (a complex carbohydrate) supplementation via randomized controlled intervention trials in childhood functional gastrointestinal disorders has demonstrated efficacy. PMID:27355647

  19. Carbohydrate Nutrition and Team Sport Performance.

    Science.gov (United States)

    Williams, Clyde; Rollo, Ian

    2015-11-01

    The common pattern of play in 'team sports' is 'stop and go', i.e. where players perform repeated bouts of brief high-intensity exercise punctuated by lower intensity activity. Sprints are generally 2-4 s long and recovery between sprints is of variable length. Energy production during brief sprints is derived from the degradation of intra-muscular phosphocreatine and glycogen (anaerobic metabolism). Prolonged periods of multiple sprints drain muscle glycogen stores, leading to a decrease in power output and a reduction in general work rate during training and competition. The impact of dietary carbohydrate interventions on team sport performance have been typically assessed using intermittent variable-speed shuttle running over a distance of 20 m. This method has evolved to include specific work to rest ratios and skills specific to team sports such as soccer, rugby and basketball. Increasing liver and muscle carbohydrate stores before sports helps delay the onset of fatigue during prolonged intermittent variable-speed running. Carbohydrate intake during exercise, typically ingested as carbohydrate-electrolyte solutions, is also associated with improved performance. The mechanisms responsible are likely to be the availability of carbohydrate as a substrate for central and peripheral functions. Variable-speed running in hot environments is limited by the degree of hyperthermia before muscle glycogen availability becomes a significant contributor to the onset of fatigue. Finally, ingesting carbohydrate immediately after training and competition will rapidly recover liver and muscle glycogen stores. PMID:26553494

  20. Blood-group-related carbohydrates are expressed in organotypic cultures of human skin and oral mucosa

    DEFF Research Database (Denmark)

    Grøn, B; Andersson, A; Dabelsteen, Erik

    1999-01-01

    Cellular maturation and migration are usually associated with changes in cell-surface carbohydrates, but the relationship between these changes and cell behaviour is at present largely unknown. To investigate whether an organotypic culture system can be used as an in vitro model to study the func......Cellular maturation and migration are usually associated with changes in cell-surface carbohydrates, but the relationship between these changes and cell behaviour is at present largely unknown. To investigate whether an organotypic culture system can be used as an in vitro model to study...... the function of cell-surface carbohydrates, we established organotypic cultures of skin and buccal mucosa. In these cultures, keratinocytes are grown at the air-liquid interface on a supporting matrix consisting of homologous fibroblasts embedded in a collagen type I gel. We examined the expression of blood......-group-related carbohydrate structures, including Lewis x, sialylated Lewis x, Lewis y, Lewis a, and Lewis b, on the surface of epithelial cells in the cultures. We compared the results with the expression of more well-established markers, including cytokeratins, integrins, bullous pemphigoid antigen and laminin, in the same...

  1. The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer

    OpenAIRE

    Zhang Shangfu; Ma Junliang; Pu Qiang; Yu Nanbin; Che Guowei; Liu Lunxu; Dai Fuqiang; Ma Lin; You Zongbing

    2010-01-01

    Abstract Background Tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time. Methods Ninety-nine patients with non-small cell lung cancer (NSC...

  2. A novel mode of carbohydrate recognition in jacalin, a Moraceae plant lectin with a beta-prism fold.

    Science.gov (United States)

    Sankaranarayanan, R; Sekar, K; Banerjee, R; Sharma, V; Surolia, A; Vijayan, M

    1996-07-01

    Jacalin, a tetrameric two-chain lectin (66,000 Mr) from jackfruit seeds, is highly specific for the tumour associated T-antigenic disaccharide. The crystal structure of jacalin with methyl-alpha-D-galactose reveals that each subunit has a three-fold symmetric beta-prism fold made up of three four-stranded beta-sheets. The lectin exhibits a novel carbohydrate-binding site involving the N terminus of the alpha-chain which is generated through a post-translational modification involving proteolysis, the first known instance where such a modification has been used to confer carbohydrate specificity. This new lectin fold may be characteristic of the Moraceae plant family. The structure provides an explanation for the relative affinities of the lectin for galactose derivatives and provides insights into the structural basis of its T-antigen specificity.

  3. The effect of Vasohibin-1 expression and tumor-associated macrophages on the angiogenesis in vitro and in vivo.

    Science.gov (United States)

    Shen, Zhanlong; Yan, Yichao; Ye, Chunxiang; Wang, Bo; Jiang, Kewei; Ye, Yingjiang; Mustonen, Harri; Puolakkainen, Pauli; Wang, Shan

    2016-06-01

    Vasohibin-1 is an intrinsic inhibitor of angiogenesis induced by VEGF-A. However, there little is known about the relationship between Vasohibin-1 expression, angiogenesis, and tumor-associated macrophages (TAMs). Vasohibin-1 expression, VEGF-A expression, microvessel density (MVD) marked with CD34, and density of cells marked with CD68 were measured in 111 paraffin-embedded tissues of gastric cancer by immunohistochemistry. The length of tube forming structures of endothelial cells and mobility rate of gastric cancer cells in Matrigel were tested by three-dimensional live cell imaging system. The effect of TAMs on the tumor growth, MVD, and Vasohibin-1 expression was measured by nude mice tumor genesis assay in vivo. We found that high Vasohibin-1 protein expression correlated significantly with worse TNM stage (P = 0.002), metastatic lymph node (P = 0.014), distant metastasis (P = 0.022), overall survival (P < 0.001), and progression-free survival (P < 0.001) compared to those with low Vasohibin-1 expression. Vasohibin-1 protein expression had statistical correlation with the MVD (r = 0.860, P < 0.001), density of CD68(+) cells (r = 0.882, P < 0.001), and VEGF-A expression (r = 0.719, P < 0.001) in the gastric cancer tissues. Decreasing Vasohibin-1 expression with siRNA increased the length of tube forming structures of endothelial cells in co-culture with endothelial cells (EA-hy923), macrophages, and gastric cancers (Hs746T). Tumor volume (P = 0.001), Vasohibin-1 (P < 0.001), and VEGF-A (P < 0.001) expression in mice inoculated with AGS and THP (10:1) was significantly higher than that with AGS alone (P = 0.001). Vasohibin-1 protein expression had statistical correlation with VEGF expression (r = 0.786, P < 0.001) and MVD (r = 0.496, P = 0.014) in gastric xenografted tumor. Therefore, Vasohibin-1 might be a potential marker of worse prognosis and therapeutic target in gastric cancer

  4. Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature.

    Directory of Open Access Journals (Sweden)

    Qiong-wen Zhang

    Full Text Available PURPOSE: Tumor associated macrophages (TAMs are considered with the capacity to have both negative and positive effects on tumor growth. The prognostic value of TAM for survival in patients with solid tumor remains controversial. EXPERIMENTAL DESIGN: We conducted a meta-analysis of 55 studies (n = 8,692 patients that evaluated the correlation between TAM (detected by immunohistochemistry and clinical staging, overall survival (OS and disease free survival (DFS. The impact of M1 and M2 type TAM (n = 5 on survival was also examined. RESULTS: High density of TAM was significantly associated with late clinical staging in patients with breast cancer [risk ratio (RR  = 1.20 (95% confidence interval (CI, 1.14-1.28] and bladder cancer [RR = 3.30 (95%CI, 1.56-6.96] and with early clinical staging in patients with ovarian cancer [RR = 0.52 (95%CI, 0.35-0.77]. Negative effects of TAM on OS was shown in patients with gastric cancer [RR = 1.64 (95%CI, 1.24-2.16], breast cancer [RR = 8.62 (95%CI, 3.10-23.95], bladder cancer [RR = 5.00 (95%CI, 1.98-12.63], ovarian cancer [RR = 2.55 (95%CI, 1.60-4.06], oral cancer [RR = 2.03 (95%CI, 1.47-2.80] and thyroid cancer [RR = 2.72 (95%CI, 1.26-5.86],and positive effects was displayed in patients with colorectal cancer [RR = 0.64 (95%CI, 0.43-0.96]. No significant effect was showed between TAM and DFS. There was also no significant effect of two phenotypes of TAM on survival. CONCLUSIONS: Although some modest bias cannot be excluded, high density of TAM seems to be associated with worse OS in patients with gastric cancer, urogenital cancer and head and neck cancer, with better OS in patients with colorectal cancer.

  5. Metabolic aspects of low carbohydrate diets and exercise

    Directory of Open Access Journals (Sweden)

    Peters Sandra

    2004-01-01

    Full Text Available Abstract Following a low carbohydrate diet, there is a shift towards more fat and less carbohydrate oxidation to provide energy to skeletal muscle, both at rest and during exercise. This review summarizes recent work on human skeletal muscle carbohydrate and fat metabolic adaptations to a low carbohydrate diet, focusing mainly on pyruvate dehydrogenase and pyruvate dehydrogenase kinase, and how these changes relate to the capacity for carbohydrate oxidation during exercise.

  6. Radiation and chemical effects on viral transformation and tumor antigen expression. Annual progress report, August 1, 1978--May 1, 1979

    International Nuclear Information System (INIS)

    Studies aimed at the biological, biochemical, and immunologic characterization of fetal antigens (EA) in hamsters and mice and locating and determining the distribution of fetal antigens in tumor tissues and in developing fetuses have been underway for several months. Progress has been made in isolating embryonic or fetal antigens from fetuses and from tumor cells. We have developed and reported a reliable lymphocyte transformation assay (LTA) which meets our needs in routinely assaying cell free tumor associated antigen (TAA) preparations from fetal and tumor cells. The assay correlated with transplantation resistance assays and has appropriate specificity. We have also developed the staph-A protein binding assay utilizing anti-serum derived against embryonic antigens present on SV40 tumor cells. In other studies, we have reported increases and perturbations in thymocytes during viral and chemical oncogenesis in hamsters, have developed a simple technique for preserving functional lymphocytes sensitized against TAA by freezing for use in our model system work, have reported the cross-reactivity of tranplantation resistance antigen on a spectrum of chemically induced tumors previously believed to only contain individually specific TSTAs and have recently reported the cross-reactivity of papovavirus induced transplantation resistance antigen in sarcoma cells induced by different viruses. We have concluded our studies of glycosyltransferases in the membranes of developing fetuses and noted no differences in their levels with advancing days of gestation using whold embryo cell populations

  7. A Truncated form of CD200 (CD200S) Expressed on Glioma Cells Prolonged Survival in a Rat Glioma Model by Induction of a Dendritic Cell-Like Phenotype in Tumor-Associated Macrophages12

    Science.gov (United States)

    Kobayashi, Kana; Yano, Hajime; Umakoshi, Akihiro; Matsumoto, Shirabe; Mise, Ayano; Funahashi, Yu; Ueno, Yoshitomo; Kamei, Yoshiaki; Takada, Yasutsugu; Kumon, Yoshiaki; Ohnishi, Takanori; Tanaka, Junya

    2016-01-01

    CD200 induces immunosuppression in myeloid cells expressing its receptor CD200R, which may have consequences for tumor immunity. We found that human carcinoma tissues express not only full-length CD200 (CD200L) but also its truncated form, CD200S. Although CD200S is reported to antagonize the immunosuppressive actions of CD200L, the role of CD200S in tumor immunity has never been investigated. We established rat C6 glioma cell lines that expressed either CD200L or CD200S; the original C6 cell line did not express CD200 molecules. The cell lines showed no significant differences in growth. Upon transplantation into the neonatal Wistar rat forebrain parenchyma, rats transplanted with C6-CD200S cells survived for a significantly longer period than those transplanted with the original C6 and C6-CD200L cells. The C6-CD200S tumors were smaller than the C6-CD200L or C6-original tumors, and many apoptotic cells were found in the tumor cell aggregates. Tumor-associated macrophages (TAMs) in C6-CD200S tumors displayed dendritic cell (DC)-like morphology with multiple processes and CD86 expression. Furthermore, CD3+, CD4+ or CD8+ cells were more frequently found in C6-CD200S tumors, and the expression of DC markers, granzyme, and perforin was increased in C6-CD200S tumors. Isolated TAMs from original C6 tumors were co-cultured with C6-CD200S cells and showed increased expression of DC markers. These results suggest that CD200S activates TAMs to become DC-like antigen presenting cells, leading to the activation of CD8+ cytotoxic T lymphocytes, which induce apoptotic elimination of tumor cells. The findings on CD200S action may provide a novel therapeutic modality for the treatment of carcinomas. PMID:27108386

  8. A Truncated form of CD200 (CD200S Expressed on Glioma Cells Prolonged Survival in a Rat Glioma Model by Induction of a Dendritic Cell-Like Phenotype in Tumor-Associated Macrophages

    Directory of Open Access Journals (Sweden)

    Kana Kobayashi

    2016-04-01

    Full Text Available CD200 induces immunosuppression in myeloid cells expressing its receptor CD200R, which may have consequences for tumor immunity. We found that human carcinoma tissues express not only full-length CD200 (CD200L but also its truncated form, CD200S. Although CD200S is reported to antagonize the immunosuppressive actions of CD200L, the role of CD200S in tumor immunity has never been investigated. We established rat C6 glioma cell lines that expressed either CD200L or CD200S; the original C6 cell line did not express CD200 molecules. The cell lines showed no significant differences in growth. Upon transplantation into the neonatal Wistar rat forebrain parenchyma, rats transplanted with C6-CD200S cells survived for a significantly longer period than those transplanted with the original C6 and C6-CD200L cells. The C6-CD200S tumors were smaller than the C6-CD200L or C6-original tumors, and many apoptotic cells were found in the tumor cell aggregates. Tumor-associated macrophages (TAMs in C6-CD200S tumors displayed dendritic cell (DC-like morphology with multiple processes and CD86 expression. Furthermore, CD3+, CD4+ or CD8+ cells were more frequently found in C6-CD200S tumors, and the expression of DC markers, granzyme, and perforin was increased in C6-CD200S tumors. Isolated TAMs from original C6 tumors were co-cultured with C6-CD200S cells and showed increased expression of DC markers. These results suggest that CD200S activates TAMs to become DC-like antigen presenting cells, leading to the activation of CD8+ cytotoxic T lymphocytes, which induce apoptotic elimination of tumor cells. The findings on CD200S action may provide a novel therapeutic modality for the treatment of carcinomas.

  9. Targeting cancer testis antigens for biomarkers and immunotherapy in colorectal cancer: Current status and challenges

    Institute of Scientific and Technical Information of China (English)

    Anil; Suri; Nirmala; Jagadish; Shikha; Saini; Namita; Gupta

    2015-01-01

    Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.

  10. Potential effect of ultrasound on carbohydrates.

    Science.gov (United States)

    Bera, Smritilekha; Mondal, Dhananjoy; Martin, Jacob T; Singh, Man

    2015-06-17

    The use of ultrasound has emerged as one of the most useful alternative energy sources for the synthesis of carbohydrate-derived biologically and pharmaceutically potential compounds. Spectacular advances have been made in the field of sonication-assisted organic reactions, which are known for producing superior yields, enhanced reactivity of the reactant, improved stereoselectivity, and shortened reaction times. Orthogonal protection-deprotection reactions and/or modification and manipulation of functional groups in carbohydrates are common synthetic steps in carbohydrate chemistry. These reaction steps can be driven by the ultrasonic energy generated by acoustic cavitation via the formation and subsequent collapse of ultrasound-induced bubbles. The ultrasound-assisted synthesis of differently functionalised monosaccharides is useful in a wide variety of applications of carbohydrate chemistry such as the glycosylation of oligosaccharides, one pot domino reactions, thioglycoside syntheses, azidoglycoside syntheses, 1,3-dipolar cycloaddition reactions, and syntheses of natural products. This review article covers ultrasound-mediated reactions on carbohydrates that have been described in the literature since 2000.

  11. A systematic review of humoral immune responses against tumor antigens.

    Science.gov (United States)

    Reuschenbach, Miriam; von Knebel Doeberitz, Magnus; Wentzensen, Nicolas

    2009-10-01

    This review summarizes studies on humoral immune responses against tumor-associated antigens (TAAs) with a focus on antibody frequencies and the potential diagnostic, prognostic, and etiologic relevance of antibodies against TAAs. We performed a systematic literature search in Medline and identified 3,619 articles on humoral immune responses and TAAs. In 145 studies, meeting the inclusion criteria, humoral immune responses in cancer patients have been analyzed against over 100 different TAAs. The most frequently analyzed antigens were p53, MUC1, NY-ESO-1, c-myc, survivin, p62, cyclin B1, and Her2/neu. Antibodies against these TAAs were detected in 0-69% (median 14%) of analyzed tumor patients. Antibody frequencies were generally very low in healthy individuals, with the exception of few TAAs, especially MUC1. For several TAAs, including p53, Her2/neu, and NY-ESO-1, higher antibody frequencies were reported when tumors expressed the respective TAA. Antibodies against MUC1 were associated with a favorable prognosis while antibodies against p53 were associated with poor disease outcome. These data suggest different functional roles of endogenous antibodies against TAAs. Although data on prediagnostic antibody levels are scarce and antibody frequencies for most TAAs are at levels precluding use in diagnostic assays for cancer early detection, there is some promising data on achieving higher sensitivity for cancer detection using panels of TAAs.

  12. Toxicities of chimeric antigen receptor T cells: recognition and management.

    Science.gov (United States)

    Brudno, Jennifer N; Kochenderfer, James N

    2016-06-30

    Chimeric antigen receptor (CAR) T cells can produce durable remissions in hematologic malignancies that are not responsive to standard therapies. Yet the use of CAR T cells is limited by potentially severe toxicities. Early case reports of unexpected organ damage and deaths following CAR T-cell therapy first highlighted the possible dangers of this new treatment. CAR T cells can potentially damage normal tissues by specifically targeting a tumor-associated antigen that is also expressed on those tissues. Cytokine release syndrome (CRS), a systemic inflammatory response caused by cytokines released by infused CAR T cells can lead to widespread reversible organ dysfunction. CRS is the most common type of toxicity caused by CAR T cells. Neurologic toxicity due to CAR T cells might in some cases have a different pathophysiology than CRS and requires different management. Aggressive supportive care is necessary for all patients experiencing CAR T-cell toxicities, with early intervention for hypotension and treatment of concurrent infections being essential. Interleukin-6 receptor blockade with tocilizumab remains the mainstay pharmacologic therapy for CRS, though indications for administration vary among centers. Corticosteroids should be reserved for neurologic toxicities and CRS not responsive to tocilizumab. Pharmacologic management is complicated by the risk of immunosuppressive therapy abrogating the antimalignancy activity of the CAR T cells. This review describes the toxicities caused by CAR T cells and reviews the published approaches used to manage toxicities. We present guidelines for treating patients experiencing CRS and other adverse events following CAR T-cell therapy. PMID:27207799

  13. Murine antigen-induced arthritis.

    NARCIS (Netherlands)

    Berg, W.B. van den; Joosten, L.A.B.; Lent, P.L.E.M. van

    2007-01-01

    Antigen induced arthritis is a unilateral T-cell driven model caused by direct injection of an antigen into the knee joint of a FCA preimmunized animal. The chronicity is determined by antigen retention in avascular structures of the joint through charge mediated binding or antibody mediated trappin

  14. Nutraceutical and pharmacological implications of marine carbohydrates.

    Science.gov (United States)

    Pallela, Ramjee

    2014-01-01

    Current day's research has been focusing much on the potential pharmacological or nutraceutical agents of selective health benefits with less toxicity. As a consequence of increased demand of nutritional supplements of great medicinal values, development of therapeutic agents from natural sources, in particular, marine environment are being considered much important. A diverse array of marine natural products containing medicinally useful nutritional substances, i.e., marine nutraceuticals have been focused to the benefit of mankind. Carbohydrates, by being constituted in considerable amount of many marine organisms display several nutraceutical and pharmaceutical behavior to defend from various diseases. Moreover, the carbohydrates from algae as well as from shellfish wastes, like chitosan and its derivatives, showed tremendous applications in biology and biomedicine. In the current chapter, several of marine carbohydrates from various marine flora and fauna have been covered with their applications and prospects in the development of nutraceuticals and pharmaceuticals.

  15. Investigation of Carbohydrate Recognition via Computer Simulation

    Directory of Open Access Journals (Sweden)

    Quentin R. Johnson

    2015-04-01

    Full Text Available Carbohydrate recognition by proteins, such as lectins and other (biomolecules, can be essential for many biological functions. Recently, interest has arisen due to potential protein and drug design and future bioengineering applications. A quantitative measurement of carbohydrate-protein interaction is thus important for the full characterization of sugar recognition. We focus on the aspect of utilizing computer simulations and biophysical models to evaluate the strength and specificity of carbohydrate recognition in this review. With increasing computational resources, better algorithms and refined modeling parameters, using state-of-the-art supercomputers to calculate the strength of the interaction between molecules has become increasingly mainstream. We review the current state of this technique and its successful applications for studying protein-sugar interactions in recent years.

  16. Protein L: a novel reagent for the detection of Chimeric Antigen Receptor (CAR expression by flow cytometry

    Directory of Open Access Journals (Sweden)

    Zheng Zhili

    2012-02-01

    Full Text Available Abstract Background There has been significant progress in the last two decades on the design of chimeric antigen receptors (CAR for adoptive immunotherapy targeting tumor-associated antigens. Structurally CARs consist of a single chain antibody fragment directed against a tumor-associated antigen fused to an extracellular spacer and transmembrane domain followed by T cell cytoplasmic signaling moieties. Currently several clinical trials are underway using gene modified peripheral blood lymphocytes (PBL with CARs directed against a variety of tumor associated antigens. Despite the improvements in the design of CARs and expansion of the number of target antigens, there is no universal flow cytometric method available to detect the expression of CARs on the surface of transduced lymphocytes. Methods Currently anti-fragment antigen binding (Fab conjugates are most widely used to determine the expression of CARs on gene-modified lymphocytes by flow cytometry. The limitations of these reagents are that many of them are not commercially available, generally they are polyclonal antibodies and often the results are inconsistent. In an effort to develop a simple universal flow cytometric method to detect the expression of CARs, we employed protein L to determine the expression of CARs on transduced lymphocytes. Protein L is an immunoglobulin (Ig-binding protein that binds to the variable light chains (kappa chain of Ig without interfering with antigen binding site. Protein L binds to most classes of Ig and also binds to single-chain antibody fragments (scFv and Fab fragments. Results We used CARs derived from both human and murine antibodies to validate this novel protein L based flow cytometric method and the results correlated well with other established methods. Activated human PBLs were transduced with retroviral vectors expressing two human antibody based CARs (anti-EGFRvIII, and anti-VEGFR2, two murine antibody derived CARs (anti-CSPG4, and anti

  17. Synthesis of chiral dopants based on carbohydrates.

    Science.gov (United States)

    Tsuruta, Toru; Koyama, Tetsuo; Yasutake, Mikio; Hatano, Ken; Matsuoka, Koji

    2014-07-01

    Chiral dopants based on carbohydrates for nematic liquid crystals were synthesized from D-glucose, and their helical twisting power (HTP) values were evaluated. The chiral dopants induced helices in the host nematic liquid crystals. An acetyl derivative having an ether-type glycosidic linkage between carbohydrate and a mesogenic moiety showed the highest HTP value of 10.4 μm(-1), while an acetyl derivative having an anomeric ester-type linkage did not show any HTP. It was surprising that this molecule had no HTP despite the presence of chirality in the molecule. A relationship between HTP and specific rotation was not observed in this study.

  18. The diagnostic value of alpha-fetoprotein, α-L-fucosidase,gamma-glutamyltransferase, alkaline phosphatase and carbohydrate antigen 19-9 in the diagnosis of primary hepatocellular carcinoma%甲胎蛋白、α-L-岩藻糖苷酶、γ-谷氨酰转移酶、碱性磷酸酶及糖类抗原19-9联合检测在原发性肝癌中的诊断价值

    Institute of Scientific and Technical Information of China (English)

    潘倩雄

    2014-01-01

    Objective To investigate the diagnostic value of alpha-fetoprotein (AFP),α-L-fucosidase(AFU),gamma-glutamyltransferase(GGT),alkaline phosphatase (ALP) and carbohydrate antigen 19-9(CA19-9) in the diagnosis of primary hepatocellular carcinoma(PHC).Methods Seventy-eight PHC patients as PHC group,76 patients with other liver diseases as other liver diseases group and 60 healthy volunteers as control group.The level of serum AFP,AFU,GGT,ALP,CA19-9 and positive rate in each group were compared.Results The level of AFP,AFU,GGT,ALP,CA19-9 in PHC group were (276.3 ±72.6)μg/L,(63.1 ± 11.7) U/L,(268.5 ±57.2) U/L,(293.4 ±61.7) U/L and (56.9 ± 12.5) μg/L,in other liver diseases group were (81.6 ± 12.1) μg/L,(28.3 ±7.3) U/L,(54.9 ±7.8) U/L,(116.5 ± 23.8) U/L and (27.8 7.1) μ g/L,in control group were (13.8 ± 2.7) μ g/L,(12.6 ± 3.9) U/L,(12.3 ± 3.2) U/L,(47.2 ± 11.3) U/L and (12.9 ± 3.4) μ g/L.The level of above index in PHC group and other liver diseases group were significantly higher than those in control group,while the level of above index in PHC group were significantly higher than those in other liver diseases group (P < 0.01 or < 0.05).The positive rate of AFP,AFU,GGT,ALP,CA19-9 in PHC group were 62.8%(49/78),79.5%(62/78),83.3% (65/78),85.9% (67/78),66.7% (52/78),and significantly higher than those in other liver diseases group[31.6%(24/76),32.9%(25/76),27.6%(21/76),22.4%(17/76),15.8 %(12/76)].The positive rate of AFP in control group was 0,the positive rate of AFU,GGT,ALP,CA19-9 in control group were 1.7% (1/60),3.3% (2/60),1.7% (1/60),8.3% (5/60),which significantly lower than those in other two groups.The positive rate of combined detection in PHC group was 100.0%(78/78),which significantly higher than that in other liver diseases group [40.8%(31/76)] and control group[8.3%(5/60)](P< 0.01).Conclusion The combined detection of AFP,AFU,GGT,ALP,CA19-9 in PHC diagnosis has a higher sensitivity,and thus to make

  19. High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study

    Energy Technology Data Exchange (ETDEWEB)

    Puig, Josep; Blasco, Gerard; Remollo, Sebastian; Hernandez, David; Pedraza, Salvador [Hospital Universitari Dr Josep Trueta, Research Unit of Diagnostic Imaging Institute (IDI), Department of Radiology [Girona Biomedical Research Institute] IDIBGI, Girona (Spain); Daunis-i-Estadella, Josep; Mateu, Gloria [University of Girona, Department of Computer Science, Applied Mathematics and Statistics, Girona (Spain); Alberich-Bayarri, Angel [La Fe Polytechnics and University Hospital, Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, Valencia (Spain); Essig, Marco [University of Manitoba, Department of Radiology, Winnipeg (Canada); Jain, Rajan [NYU School of Medicine, Division of Neuroradiology, Department of Radiology, New York, NY (United States); Puigdemont, Montserrat [Hospital Universitari Dr Josep Trueta, Catalan Institute of Oncology (ICO), Hospital Cancer Registry, Girona (Spain); Sanchez-Gonzalez, Javier [Philips Healthcare Iberica, Madrid (Spain); Wintermark, Max [Stanford University, Department of Radiology, Neuroradiology Division, Palo Alto, CA (United States)

    2016-01-15

    The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival. (orig.)

  20. Neuroendoscopic biopsy and the treatment of tumor-associated hydrocephalus of the ventricular and paraventricular region in pediatric patients: a nationwide study in Japan.

    Science.gov (United States)

    Miwa, Tomoru; Hayashi, Nakamasa; Endo, Shunro; Ohira, Takayuki

    2015-10-01

    A neuroendoscopic biopsy is a minimally invasive and useful procedure for the diagnosis and initial management of tumor-associated hydrocephalus. We describe the nationwide investigation of the current status of neuroendoscopic biopsy for intra- and paraventricular tumors in children, as well as the treatment of tumor-associated hydrocephalus in pediatric patients. The main items examined included the patient's age and sex, location of the tumor, pathological diagnosis, complications, treatment and efficacy of treatment of the tumor-associated hydrocephalus, and the dissemination during the postoperative course. Two hundred twenty-one pediatric patients (mean 8.6 years) from 67 institutions were registered. Endoscopic tumor biopsies were performed in 206 patients (93.2 %), and a histopathological diagnosis could be performed in 195 of these 206 patients (94.7 %). The most frequently histopathologically diagnosed tumor was a germ cell tumor (41.5 %), followed by astrocytic tumors (24.1 %) and cystic lesions (15.9 %). Associated hydrocephalus was observed in 177 patients (80.1 %), 101 of whom underwent endoscopic third ventriculostomy (ETV). The efficacy rate of the ETV in the perioperative period was 99.0 %, and the long-term response rate was 90.1 %. Perioperative complications other than fever were found in 24 patients (10.9 %). In the statistical analysis, pediatric long-term response rate to ETV (p = 0.025) showed significantly more favorable results for pediatric than adult patients (p < 0.05). Neuroendoscopic procedures involving pediatric intra- and paraventricular tumors were considered to be very useful, with a low incidence of complication, and were associated with higher safety.

  1. High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study

    International Nuclear Information System (INIS)

    The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival. (orig.)

  2. Imaging of bronchial carcinoid tumors associated to Cushing syndrome with 111In-Octreoscan scintigraphy and immunoscintigraphy with anti-chromogranin monoclonal antibodies. Report of two cases.

    Science.gov (United States)

    Carretta, A; Chiesa, G; Magnani, P; Songini, C; Melloni, G; Zannini, P; Grossi, A

    1997-04-01

    Bronchial carcinoid tumors are neuroendocrine neoplasms capable of expressing somatostatin receptors and of secreting neuromediators such as ACTH and chromogranins. Radiologic appearance is usually non-specific and has to be distinguished from benign pulmonary nodules and other malignant diseases. Standard radiological techniques have limited accuracy in the evaluation of such lesions. Radioisotopic imaging techniques may increase the specificity of diagnostic assessment. The role of immunoscintigraphy with anti-chromogranin A and B monoclonal antibodies (MoAbs) and of 111In-Octreoscan scintigraphy is evaluated in two cases of bronchial carcinoid tumors associated to Cushing syndrome. PMID:9201136

  3. Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells

    OpenAIRE

    Li, Hongzhong; Yang, Bing; Huang, Jing; Lin, Yong; Xiang, Tingxiu; Wan, Jingyuan; Li, Hongyuan; Chouaib, Salem; Ren, Guosheng

    2015-01-01

    Tumor-associated macrophages (TAMs) play an important role in cancer cell survival, however, the mechanism of which remains elusive. In this study, we found that COX-2 was abundantly expressed in breast TAMs, which was correlated to poor prognosis in breast cancer patients. Ectopic over-expression of COX-2 in TAMs enhanced breast cancer cell survival both in vitro and in vivo. COX-2 in TAMs was determined to be essential for the induction and maintenance of M2-phenotype macrophage polarity. C...

  4. Transient phosphorylation of tumor associated microtubule associated protein (TMAP)/cytoskeleton associated protein 2 (CKAP2) at Thr-596 during early phases of mitosis

    OpenAIRE

    Hong, Kyung Uk; Choi, Yong-Bock; Lee, Jung-Hwa; Kim, Hyun-Jun; Kwon, Hye-Rim; Seong, Yeon-Sun; KIM, HEUNG TAE; Park, Joobae; Bae, Chang-Dae; Hong, Kyeong-Man

    2008-01-01

    Tumor associated microtubule associated protein (TMAP), also known as cytoskeleton associated protein 2 (CKAP2) is a mitotic spindle-associated protein whose expression is cell cycle-regulated and also frequently deregulated in cancer cells. Two monoclonal antibodies (mAbs) against TMAP/CKAP2 were produced: B-1-13 and D-12-3. Interestingly, the reactivity of mAb D-12-3 to TMAP/CKAP2 was markedly decreased specifically in mitotic cell lysate. The epitope mapping study showed that mAb D-12-3 re...

  5. Identification of transcripts encoding a parathyroid hormone-like peptide in messenger RNAs from a variety of human and animal tumors associated with humoral hypercalcemia of malignancy.

    OpenAIRE

    Ikeda, K.; Mangin, M; Dreyer, B E; Webb, A C; Posillico, J T; Stewart, A F; Bander, N. H.; Weir, E C; Insogna, K. L.; Broadus, A E

    1988-01-01

    The syndrome of humoral hypercalcemia of malignancy (HHM) appears to be mediated in many instances by a parathyroid hormone-like peptide, which has recently been purified, sequenced, and cloned. Using a probe representing the coding region of the human PTH-like peptide, we examined by Northern analysis poly (A)+ RNA from a variety of human and animal tumors associated with HHM. Hybridizing transcripts were identified in mRNA from each of 12 human and each of four animal HHM-associated tumors,...

  6. Carcinoembryonic antigen continuous epitopes determined by the spot method.

    Science.gov (United States)

    Solassol, I; Granier, C; Pèlegrin, A

    2001-01-01

    Carcinoembryonic antigen (CEA) is a heavily glycosylated tumor-associated protein with an N-A1-B1-A2-B2-A3-B3 domain structure. Circulating CEA immunoassays are used for monitoring digestive cancer patients, and radiolabeled anti-CEA monoclonal antibodies (MAb) are used for the diagnosis and therapy of CEA-positive tumors. The five major nonoverlapping epitopes (Gold 1-5) have been broadly correlated with the domain organization, but there is no precise localization of the epitopes at the sequence level. In an attempt to identify the peptide sequences corresponding to the five Gold epitopes on the CEA molecule, we prepared a set of 227 overlapping fifteen-mer peptides corresponding to the complete CEA sequence with the SPOT method. Using five high affinity MAbs directed against the five CEA Gold epitopes, we demonstrated that none of these epitopes could be mimicked by a fifteen-mer peptide sequence. However, using rabbit and goat anti-CEA sera, we identified six major continuous antigenic regions. All are included in the Ig-like domains of the CEA: two in the A1 domain (residues 120-134 and 153-164), one each in the A2 (329-337) and A3 domains (508-513), one at the junction between the A3 and B3 domains (553-561) and one in the B3 domain (565-573). A very homologous sequence (common residues VSPRL) was mapped in each of the three A domains. Thus, in terms of occurrence of continuous epitopes, the Ig-like domains A1, A2, A3 and B3 seem to be the most antigenic parts of CEA. These peptide sequences should be good candidates for the future development of site-specific anti-CEA MAbs. PMID:11275797

  7. Separation and quantification of microalgal carbohydrates.

    Science.gov (United States)

    Templeton, David W; Quinn, Matthew; Van Wychen, Stefanie; Hyman, Deborah; Laurens, Lieve M L

    2012-12-28

    Structural carbohydrates can constitute a large fraction of the dry weight of algal biomass and thus accurate identification and quantification is important for summative mass closure. Two limitations to the accurate characterization of microalgal carbohydrates are the lack of a robust analytical procedure to hydrolyze polymeric carbohydrates to their respective monomers and the subsequent identification and quantification of those monosaccharides. We address the second limitation, chromatographic separation of monosaccharides, here by identifying optimum conditions for the resolution of a synthetic mixture of 13 microalgae-specific monosaccharides, comprised of 8 neutral, 2 amino sugars, 2 uronic acids and 1 alditol (myo-inositol as an internal standard). The synthetic 13-carbohydrate mix showed incomplete resolution across 11 traditional high performance liquid chromatography (HPLC) methods, but showed improved resolution and accurate quantification using anion exchange chromatography (HPAEC) as well as alditol acetate derivatization followed by gas chromatography (for the neutral- and amino-sugars only). We demonstrate the application of monosaccharide quantification using optimized chromatography conditions after sulfuric acid analytical hydrolysis for three model algae strains and compare the quantification and complexity of monosaccharides in analytical hydrolysates relative to a typical terrestrial feedstock, sugarcane bagasse. PMID:23177152

  8. Nutrient and carbohydrate partitioning in sorghum stover

    International Nuclear Information System (INIS)

    Sorghum [Sorghum bicolor (L.) Moench] stover has been demonstrated to be a potential biomass energy source. Complete aboveground crop removal, however, can result in soil degradation. Differential dry matter, nutrient, and carbohydrate partitioning by sorghum cultivars may allow management strategies that return certain parts to the field while removing other portions for alternative uses, such as energy production. A field study was conducted to determine N,P,K, nonstructural carbohydrate, cellulose hemicellulose, and lignin distributions in stover of three diverse sorghum cultivars of differing harvest indices. Determinations were based on total vegetative biomass; total blades; total stalks; and upper middle, and lower blades and stalks. Concentrations of N and P were higher in blades than stalks and generally declines from upper to lower stover parts. Large carbohydrate and lignin concentration differences were observed on the basis of cultivar and stover part. Greater nutrient partitioning to the upper third of the intermediate and forage-type sorghum stovers was observed as compared to the conventional grain cultivar. Stover carbohydrates for all cultivars were mainly contained in the lower two-thirds of the stalk fraction. A system was proposed for returning upper stover portion to soil, while removing remaining portions for alternative uses

  9. The diagenesis of carbohydrates by hydrogen sulfide

    Science.gov (United States)

    Mango, Frank D.

    1983-08-01

    Carbohydrates react with hydrogen sulfide under low temperature (100° to 200°C) yielding a variety of organosulfur compounds including thiophenes, thiols, sulfides and sulfones. A polymer is also produced, whose elemental composition is within the range of natural coals. When reductive dehydration is carried out in the presence of hydrocarbon, organosulfur compounds are formed in the carbon number range of the hydrocarbon used. In these processes, an active hydrogen transfer catalyst is produced which facilitates the passage of hydrogen between normal paraffins and saccharide units, distributing sulfur between these two families primarily in the form of thiophene rings. The simplicity of these systems - H 2S, carbohydrates, H 2O, hydrocarbon - and the facility of the chemistry would suggest that the carbohydrates and hydrogen sulfide may be important agents in the diagenetic processes leading to petroleum and coal. Carbohydrate reduction by hydrogen sulfide may constitute an important route through which certain organosulfur compounds found in petroleum and coal entered these materials in early diagenesis.

  10. Saturated fat, carbohydrates and cardiovascular disease

    NARCIS (Netherlands)

    Kuipers, R. S.; de Graaf, D. J.; Luxwolda, M. F.; Muskiet, M. H. A.; Dijck-Brouwer, D. A. J.; Muskiet, F. A. J.

    2011-01-01

    The dietary intake of saturated fatty acids (SAFA) is associated with a modest increase in serum total cholesterol, but not with cardiovascular disease (CVD). Replacing dietary SAFA with carbohydrates (CHO), notably those with a high glycaemic index, is associated with an increase in CVD risk in obs

  11. General Properties, Occurrence, and Preparation of Carbohydrates

    Science.gov (United States)

    Robyt, John F.

    D-Glucose and its derivatives and analogues, N-acetyl-D-glucosamine, N-acetyl-D-muramic acid, D-glucopyranosyl uronic acid, and D-glucitol represent 99.9% of the carbohydrates on the earth. D-Glucose is found in the free state in human blood and in the combined state in disaccharides, sucrose, lactose, and α,α-trehalose, in cyclic dextrins, and in polysaccharides, starch, glycogen, cellulose, dextrans; N-acetyl-D-glucosamine and an analogue N-acetyl-D-muramic acid are found in bacterial cell wall polysaccharide, murein, along with teichoic acids made up of poly-glycerol or -ribitol phosphodiesters. Other carbohydrates, D-mannose, D-mannuronic acid, D-galactose, N-acetyl-D-galactosamine, D-galacturonic acid, D-iduronic acid, L-guluronic acid, L-rhamnose, L-fucose, D-xylose, and N-acetyl-D-neuraminic acid are found in glycoproteins, hemicelluloses, glycosaminoglycans, and polysaccharides of plant exudates, bacterial capsules, alginates, and heparin. D-Ribofuranose-5-phosphate is found in many coenzymes and is the backbone of RNAs (ribonucleic acid), and 2-deoxy-D-ribofuranose-5-phosphate is the backbone of DNA (deoxyribonucleic acid). D-Fructofuranose is found in sucrose, inulin, and levan. The general properties and occurrence of these carbohydrates and general methods of isolation and preparation of carbohydrates are presented.

  12. Hydrogen and methane breath tests for evaluation of resistant carbohydrates

    DEFF Research Database (Denmark)

    Rumessen, J J

    1992-01-01

    This review considers in detail the background, principles, techniques, limitations and advantages of the hydrogen and methane breath tests. Resistant food carbohydrates, defined as dietary carbohydrates partly or totally escaping small intestinal assimilation, are fermented in the human colon. T...

  13. Exercise and Regulation of Carbohydrate Metabolism.

    Science.gov (United States)

    Mul, Joram D; Stanford, Kristin I; Hirshman, Michael F; Goodyear, Laurie J

    2015-01-01

    Carbohydrates are the preferred substrate for contracting skeletal muscles during high-intensity exercise and are also readily utilized during moderate intensity exercise. This use of carbohydrates during physical activity likely played an important role during the survival of early Homo sapiens, and genes and traits regulating physical activity, carbohydrate metabolism, and energy storage have undoubtedly been selected throughout evolution. In contrast to the life of early H. sapiens, modern lifestyles are predominantly sedentary. As a result, intake of excessive amounts of carbohydrates due to the easy and continuous accessibility to modern high-energy food and drinks has not only become unnecessary but also led to metabolic diseases in the face of physical inactivity. A resulting metabolic disease is type 2 diabetes, a complex endocrine disorder characterized by abnormally high concentrations of circulating glucose. This disease now affects millions of people worldwide. Exercise has beneficial effects to help control impaired glucose homeostasis with metabolic disease, and is a well-established tool to prevent and combat type 2 diabetes. This chapter focuses on the effects of exercise on carbohydrate metabolism in skeletal muscle and systemic glucose homeostasis. We will also focus on the molecular mechanisms that mediate the effects of exercise to increase glucose uptake in skeletal muscle. It is now well established that there are different proximal signaling pathways that mediate the effects of exercise and insulin on glucose uptake, and these distinct mechanisms are consistent with the ability of exercise to increase glucose uptake in the face of insulin resistance in people with type 2 diabetes. Ongoing research in this area is aimed at defining the precise mechanism by which exercise increases glucose uptake and insulin sensitivity and the types of exercise necessary for these important health benefits.

  14. Energy and carbohydrate for training and recovery.

    Science.gov (United States)

    Burke, Louise M; Loucks, Anne B; Broad, Nick

    2006-07-01

    Soccer players should achieve an energy intake that provides sufficient carbohydrate to fuel the training and competition programme, supplies all nutrient requirements, and allows manipulation of energy or nutrient balance to achieve changes in lean body mass, body fat or growth. Although the traditional culture of soccer has focused on carbohydrate intake for immediate match preparation, top players should adapt their carbohydrate intake on a daily basis to ensure adequate fuel for training and recovery between matches. For players with a mobile playing style, there is sound evidence that dietary programmes that restore and even super-compensate muscle glycogen levels can enhance activity patterns during matches. This will presumably also benefit intensive training, such as twice daily practices. As well as achieving a total intake of carbohydrate commensurate with fuel needs, the everyday diet should promote strategic intake of carbohydrate and protein before and after key training sessions to optimize the adaptations and enhance recovery. The achievement of the ideal physique for soccer is a long-term goal that should be undertaken over successive years, and particularly during the off-season and pre-season. An increase in lean body mass or a decrease in body fat is the product of a targeted training and eating programme. Consultation with a sports nutrition expert can assist soccer players to manipulate energy and nutrient intake to meet such goals. Players should be warned against the accidental or deliberate mismatch of energy intake and energy expenditure, such that energy availability (intake minus the cost of exercise) falls below 125 kJ (30 kcal) per kilogram of fat-free mass per day. Such low energy availability causes disturbances to hormonal, metabolic, and immune function. PMID:16766497

  15. Carbohydrate deficient transferrin (CDT) in alcoholic cirrhosis: a kinetic study

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Grønbaek, M; Møller, Søren;

    1997-01-01

    controls (n = 8), which indicates a slow turnover rate of carbohydrate deficient transferrin. Food ingestion did not affect the circulating level of carbohydrate deficient transferrin, and the analysis of carbohydrate deficient transferrin was almost unaffected by the presence of ethanol in plasma within...... alcohol intake, but the overlap is substantial in patients with cirrhosis. Carbohydrate deficient transferrin has a low turnover rate in both patients with cirrhosis and normals....

  16. Slime Production and Expression of the Slime-Associated Antigen by Staphylococcal Clinical Isolates

    OpenAIRE

    Ammendolia, M. G.; R. Di Rosa; Montanaro, L; Arciola, C. R.; Baldassarri, L.

    1999-01-01

    The ability to produce slime and to express a slime-associated antigen was examined in a collection of staphylococcal clinical isolates. Slime-producing strains were found among coagulase-negative staphylococci in percentages comparable to those reported in other studies; surprisingly, a high percentage of Staphylococcus aureus strains also were able to produce this extracellular material. In the latter case, this ability was strongly dependent on the presence of an additional carbohydrate so...

  17. Genogroup IV and VI Canine Noroviruses Interact with Histo-Blood Group Antigens

    OpenAIRE

    Caddy, Sarah ,; Breiman, Adrien; Le Pendu, Jacques; Goodfellow, Ian

    2014-01-01

    ABSTRACT Human noroviruses (HuNV) are a significant cause of viral gastroenteritis in humans worldwide. HuNV attaches to cell surface carbohydrate structures known as histo-blood group antigens (HBGAs) prior to internalization, and HBGA polymorphism among human populations is closely linked to susceptibility to HuNV. Noroviruses are divided into 6 genogroups, with human strains grouped into genogroups I (GI), II, and IV. Canine norovirus (CNV) is a recently discovered pathogen in dogs, with s...

  18. Dietary influences over proliferating cell nuclear antigen expression in the locust midgut

    OpenAIRE

    Zudaire, E. (Enrique); Simpson, S J; Illa, I.; Montuenga, L M

    2004-01-01

    We have studied the influence of variations in dietary protein (P) and digestible carbohydrate (C), the quantity of food eaten, and insect age during the fifth instar on the expression of the proliferating cell nuclear antigen (PCNA) in the epithelial cells of the midgut (with special reference to the midgut caeca) in the African migratory locust, Locusta migratoria. Densitometric analysis of PCNA-immunostained cells was used as an indirect measure of the levels of expression of PCNA, and a P...

  19. Carcino-Embryonic Antigen

    International Nuclear Information System (INIS)

    Tumour marker analysis has increased our understanding of the presence of tumours in the body. Carcino-embryonic antigen, CEA, is one of the best studied tumour markers and has proved an ideal diagnostic adjuvant. It has helped in quantifying the amount of disease present in a patient and thence to make accurate prognosis on the various diagnosed ailments. At UCH, it is observed that there is an increase in cancer related ailments and therefore the need for early diagnosis is more compelling in our environment to mitigate future cost of managing advanced manifestation

  20. Optimized tumor cryptic peptides: the basis for universal neo-antigen-like tumor vaccines.

    Science.gov (United States)

    Menez-Jamet, Jeanne; Gallou, Catherine; Rougeot, Aude; Kosmatopoulos, Kostas

    2016-07-01

    The very impressive clinical results recently obtained in cancer patients treated with immune response checkpoint inhibitors boosted the interest in immunotherapy as a therapeutic choice in cancer treatment. However, these inhibitors require a pre-existing tumor specific immune response and the presence of tumor infiltrating T cells to be efficient. This immune response can be triggered by cancer vaccines. One of the main issues in tumor vaccination is the choice of the right antigen to target. All vaccines tested to date targeted tumor associated antigens (TAA) that are self-antigens and failed to show a clinical efficacy because of the immune self-tolerance to TAA. A new class of tumor antigens has recently been described, the neo-antigens that are created by point mutations of tumor expressing proteins and are recognized by the immune system as non-self. Neo-antigens exhibit two main properties: they are not involved in the immune self-tolerance process and are immunogenic. However, the majority of the neo-antigens are patient specific and their use as cancer vaccines requires their previous identification in each patient individualy that can be done only in highly specialized research centers. It is therefore evident that neo-antigens cannot be used for patient vaccination worldwide. This raises the question of whether we can find neo-antigen like vaccines, which would not be patient specific. In this review we show that optimized cryptic peptides from TAA are neo-antigen like peptides. Optimized cryptic peptides are recognized by the immune system as non-self because they target self-cryptic peptides that escape self-tolerance; in addition they are strongly immunogenic because their sequence is modified in order to enhance their affinity for the HLA molecule. The first vaccine based on the optimized cryptic peptide approach, Vx-001, which targets the widely expressed tumor antigen telomerase reverse transcriptase (TERT), has completed a large phase I clinical

  1. Immunogenetic mechanisms driving norovirus GII.4 antigenic variation.

    Directory of Open Access Journals (Sweden)

    Lisa C Lindesmith

    Full Text Available Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials. To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal antibodies (mAbs characterized for reactivity to a panel of time-ordered GII.4 virus-like particles (VLPs. Reflecting the complex exposure history of the volunteer, human anti-GII.4 mAbs grouped into three VLP reactivity patterns; ancestral (1987-1997, contemporary (2004-2009, and broad (1987-2009. NVB 114 reacted exclusively to the earliest GII.4 VLPs by EIA and blockade. NVB 97 specifically bound and blocked only contemporary GII.4 VLPs, while NBV 111 and 43.9 exclusively reacted with and blocked variants of the GII.4.2006 Minerva strain. Three mAbs had broad GII.4 reactivity. Two, NVB 37.10 and 61.3, also detected other genogroup II VLPs by EIA but did not block any VLP interactions with carbohydrate ligands. NVB 71.4 cross-neutralized the panel of time-ordered GII.4 VLPs, as measured by VLP-carbohydrate blockade assays. Using mutant VLPs designed to alter predicted antigenic epitopes, two evolving, GII.4-specific, blockade epitopes were mapped. Amino acids 294-298 and 368-372 were required for binding NVB 114, 111 and 43.9 mAbs. Amino acids 393-395 were essential for binding NVB 97, supporting earlier correlations between antibody blockade escape and carbohydrate binding variation. These data inform VLP vaccine design, provide a strategy for expanding the cross-blockade potential of chimeric VLP vaccines, and identify an antibody with broadly neutralizing therapeutic potential for the treatment of human disease. Moreover, these data support the hypothesis that GII.4 norovirus evolution is heavily influenced by antigenic variation of neutralizing

  2. Cancer testis antigen and immunotherapy

    Directory of Open Access Journals (Sweden)

    Krishnadas DK

    2013-04-01

    Full Text Available Deepa Kolaseri Krishnadas, Fanqi Bai, Kenneth G Lucas Department of Pediatrics, Division of Hematology/Oncology, University of Louisville, KY, USA Abstract: The identification of cancer testis (CT antigens has been an important advance in determining potential targets for cancer immunotherapy. Multiple previous studies have shown that CT antigen vaccines, using both peptides and dendritic cell vaccines, can elicit clinical and immunologic responses in several different tumors. This review details the expression of melanoma antigen family A, 1 (MAGE-A1, melanoma antigen family A, 3 (MAGE-A3, and New York esophageal squamous cell carcinoma-1 (NY-ESO-1 in various malignancies, and presents our current understanding of CT antigen based immunotherapy. Keywords: cancer testis antigens, immunotherapy, vaccine

  3. Development and validation of a high throughput system for discovery of antigens for autoantibody detection.

    Directory of Open Access Journals (Sweden)

    Isabel K Macdonald

    Full Text Available An assay employing a panel of tumor-associated antigens has been validated and is available commercially (EarlyCDT®-Lung to aid the early detection of lung cancer by measurement of serum autoantibodies. The high throughput (HTP strategy described herein was pursued to identify new antigens to add to the EarlyCDT-Lung panel and to assist in the development of new panels for other cancers. Two ligation-independent cloning vectors were designed and synthesized, producing fusion proteins suitable for the autoantibody ELISA. We developed an abridged HTP version of the validated autoantibody ELISA, determining that results reflected the performance of the EarlyCDT assay, by comparing results on both formats. Once validated this HTP ELISA was utilized to screen multiple fusion proteins prepared on small-scale, by a HTP expression screen. We determined whether the assay performance for these HTP protein batches was an accurate reflection of the performance of R&D or commercial batches. A HTP discovery platform for the identification and optimal production of tumor-associated antigens which detects autoantibodies has been developed and validated. The most favorable conditions for the exposure of immunogenic epitopes were assessed to produce discriminatory proteins for use in a commercial ELISA. This process is rapid and cost-effective compared to standard cloning and screening technologies and enables rapid advancement in the field of autoantibody assay discovery. This approach will significantly reduce timescale and costs for developing similar panels of autoantibody assays for the detection of other cancer types with the ultimate aim of improved overall survival due to early diagnosis and treatment.

  4. Structural studies on some capsular antigens from Escherichia Coli and Klebsiella

    International Nuclear Information System (INIS)

    A review of the structural studies of bacterial capsular polysaccharides (K-antigens) from Escherichia coli (E.coli) and Klebsiella is presented. There is a general trend in the structural elucidation of polysaccharides towards the analysis of higher oligosaccharides. This trend has been facilitated by advances in modern instrumental techniques for the analysis of oligosaccharides, for example, high-performance liquid chromatography, mass spectometry and nuclear magnetic resonance spectroscopy. The structural elucidations of the capsular polysaccharides from E. Coli K37 and K55, and Klebsiella K39 are reported. This elucidation of K-antigens provides an insight into the response of mammalian immune systems to antigenic stimuli. The usefulness of bacteriophage degradation as a technique for the structural elucidation of polysaccharides containing repeating unit structures is emphasized. The bacteriophage degradation of E. coli K55 polysaccharide illustrates that bacteriophage-borne enzymes may be used to degrade chemically related carbohydrate materials. The bacteriophage technique for the structural elucidation of the Klebsiella K39 polysaccharide also illustrates the advantages of this technique where the polysaccharide contains labile glycosidic bonds which are readily cleaved during standard chemical analysis. The enzymatic degradation of polysaccharides allows high yields of specific oligosaccharides to be recovered. The feasibility of analysing small amounts of carbohydrate material has become realistic due to improved instrumental capabilities. At the same time, more detailed information concerning the fine structure of known carbohydrate materials can be elucidated. 421 refs., 56 figs., 16 tabs

  5. Human leucocyte antigens in tympanosclerosis.

    Science.gov (United States)

    Dursun, G; Acar, A; Turgay, M; Calgüner, M

    1997-02-01

    This study was designed to evaluate the association between certain HLA antigens and tympanosclerosis. The serum concentrations of HLA antigens were measured by a microlymphocytotoxicity technique in patients with tympanosclerosis and compared with a healthy control group. The serum levels of HLA-B35 and -DR3 were significantly higher in the patients with tympanosclerosis. This result suggests that certain types of HLA antigens may play an important role as an indicator or mediator in the pathogenesis of tympanosclerosis. PMID:9088683

  6. Role of carbohydrate metabolism in grass tetany

    Energy Technology Data Exchange (ETDEWEB)

    Miller, J.K.; Madsen, F.C.; Lentz, D.E.; Hansard, S.L.

    1977-01-01

    Clinical hypomagnesemia is confined primarily to beef cattle in the United States but also occurs in dairy cattle in other countries, probably due to different management practices. During periods when grass tetany is likely, early vegetative temperate zone grasses are usually low in total readily available carbohydrates and magnesium but high in potassium and nitrogen. The tetany syndrome may include hypoglycemia and ketosis, suggesting an imbalance in intermediary energy metabolism. Many enzyme systems critical to cellular metabolism, including those which hydrolyze and transfer phosphate groups, are activated by Mg. Thus, by inference, Mg is required for normal glucose utilization, fat, protein, nucleic acid and coenzyme synthesis, muscle contraction, methyl group transfer, and sulfate, acetate, and formate activation. Numerous clinical and experimental studies suggest an intimate relationship between metabolism of Mg and that of carbohydrate, glucagon, and insulin. The objective is to review this literature and suggest ways in which these relationships might contribute to a chain of events leading to grass tetany.

  7. Solubility of carbohydrates in heavy water.

    Science.gov (United States)

    Cardoso, Marcus V C; Carvalho, Larissa V C; Sabadini, Edvaldo

    2012-05-15

    The solubility of several mono-(glucose and xylose), di-(sucrose and maltose), tri-(raffinose) and cyclic (α-cyclodextrin) saccharides in H(2)O and in D(2)O were measured over a range of temperatures. The solution enthalpies for the different carbohydrates in the two solvents were determined using the vant' Hoff equation and the values in D(2)O are presented here for the first time. Our findings indicate that the replacement of H(2)O by D(2)O remarkably decreases the solubilities of the less soluble carbohydrates, such as maltose, raffinose and α-cyclodextrin. On the other hand, the more soluble saccharides, glucose, xylose, and sucrose, are practically insensitive to the H/D replacement in water. PMID:22480785

  8. Carbohydrate drugs%糖类药物

    Institute of Scientific and Technical Information of China (English)

    杜晓光; 耿美玉

    2011-01-01

    As an important biological information molecules and high-density information carriers, sugar chain involved in almost all life processes in living beings, especially in cell differentiation, development, immunity, aging, cancer, signal transduction and other basic life activities and diseases. For the bioactivities of carbohydrates, carbohydrate drugs had been widely used in anti-tumor, Alzheimer's disease, immune, anti-virus, and other diseases. And the use of carbohydrates is still expanding. Therefore, the various bioactivities and low toxicity endow carbohydrates broad prospects.%糖链作为重要的生物信息分了和高密度的信息载体,参与细胞生物几乎所有的生命过程,特别是在细胞分化、发育、免疫、老化、癌变、信息传递等生命基础活动和重大疾病过程中起着特异性的识别、介导与调控作用.由于糖类物质的多种多样的生物活性,糖类药物在抗肿瘤、老年痴呆、免疫、抗病毒等多个重大疾病领域广泛应用,而且其使用范围还在不断开拓中.因此,糖类药物生物活性多样,毒副作用低,具有广阔的发展前景.

  9. Direct synthesis of methyl phosphoramidates in carbohydrates.

    Science.gov (United States)

    Dhurandhare, Vijay M; Mishra, Girija Prasad; Lam, Sarah; Wang, Cheng-Chung

    2015-09-28

    A direct installation of a methyl phosphoramidate group by using methyl benzylphosphoramidochloridate into carbohydrates and amino acid is described. This one-step synthesis is efficient for both primary and secondary alcohols and exhibited excellent regioselectivity and functional group compatibility. Formation of a single diastereomer is observed in certain cases. The N-benzyl protecting group on methyl phosphoramidates is easily removed under mild conditions.

  10. Analysis and validation of carbohydrate three-dimensional structures

    International Nuclear Information System (INIS)

    The article summarizes the information that is gained from and the errors that are found in carbohydrate structures in the Protein Data Bank. Validation tools that can locate these errors are described. Knowledge of the three-dimensional structures of the carbohydrate molecules is indispensable for a full understanding of the molecular processes in which carbohydrates are involved, such as protein glycosylation or protein–carbohydrate interactions. The Protein Data Bank (PDB) is a valuable resource for three-dimensional structural information on glycoproteins and protein–carbohydrate complexes. Unfortunately, many carbohydrate moieties in the PDB contain inconsistencies or errors. This article gives an overview of the information that can be obtained from individual PDB entries and from statistical analyses of sets of three-dimensional structures, of typical problems that arise during the analysis of carbohydrate three-dimensional structures and of the validation tools that are currently available to scientists to evaluate the quality of these structures

  11. Precocious puberty secondary to a mixed germ cell-sex cord-stromal tumor associated with an ovarian yolk sac tumor: a case report

    Directory of Open Access Journals (Sweden)

    Metwalley Kotb

    2012-06-01

    Full Text Available Abstract Introduction Ovarian tumors are the least common cause of sexual precocity in girls. Mixed germ cell-sex cord-stromal tumors associated with a yolk sac tumor of the ovary are rare neoplasms, of which only a small number of well-documented cases have been described so far. Here, we report precocious puberty in a four-year-old Egyptian girl caused by a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary. Case presentation A four-year-old Egyptian girl was referred to our pediatric endocrinology unit for evaluation of bilateral breast budding, pubic hair and vaginal bleeding. On examination, we found that her breast enlargement and pubic hair were compatible with Tanner III. A thorough workup revealed a large mass in her right ovary. Magnetic resonance imaging ofher brain showed that her pituitary gland was normal. A hormonal assay revealed high levels of estradiol, 280 to 375pmol/L; progesterone, 5.3 nmol/L; testosterone 38.9 pg/mL; and androstenedione, 4.1 ng/mL. Her basal and stimulated levels of luteinizing hormone and follicle-stimulating hormone were low. Tumor markers levels were high, with a total inhibin of 1,069U/L and an alpha-fetoprotein of 987 μg/L. Her chromosomes were normal (46XX. Our patient underwent an explorative laparotomy and a solid tumor localized to her right ovary was identified. A right salpingo-oophorectomy was performed and the histopathological diagnosis was a mixed germ cell-sex cord-stromal tumorwith a yolk sac tumor of the ovary. Postoperatively, she was started on treatment with chemotherapy. Our patient is doing well without evidence of tumor recurrence or metastasis during eight months of postoperative follow-up. Conclusion Although a mixed germ cell-sex cord-stromal tumor associated with a yolk sac tumor of the ovary is a rare occurrence, it should be considered in the differential diagnosis for a prepubescent girl with an abdominal mass and precocious puberty.

  12. Antigen antibody interactions

    CERN Document Server

    DeLisi, Charles

    1976-01-01

    1. 1 Organization of the Immune System One of the most important survival mechanisms of vertebrates is their ability to recognize and respond to the onslaught of pathogenic microbes to which they are conti- ously exposed. The collection of host cells and molecules involved in this recognition­ 12 response function constitutes its immune system. In man, it comprises about 10 cells 20 (lymphocytes) and 10 molecules (immunoglobulins). Its ontogenic development is c- strained by the requirement that it be capable of responding to an almost limitless variety of molecular configurations on foreign substances, while simultaneously remaining inert to those on self components. It has thus evolved to discriminate, with exquisite precision, between molecular patterns. The foreign substances which induce a response, called antigens, are typically large molecules such as proteins and polysaccharides. The portions of these with which immunoglobulins interact are called epitopes or determinants. A typical protein epitope m...

  13. UV-B radiation does not limit carbohydrate level and carbohydrate metabolism in cucumber leaves

    Directory of Open Access Journals (Sweden)

    Magdalena Rybus-Zając

    2014-08-01

    Full Text Available Cucumber is a vegetable exhibiting relatively high sensitivity to environmental stress factors. When it is grown outdoors, from early stages of development there is a real risk of exposure to elevated UV-B radiation. In order to explain the effects of time-dependent UV-B doses on carbohydrate level and metabolism, the photosynthetic activity, accumulation of carbohydrates and activities of carbohydrate-related enzymes were determined in the cucumber leaves. Elevated UV-B radiation led to an increase in the rate of photosynthesis, which was reflected by an increase in SPAD values. Higher photosynthetic activity resulted in an increase in levels of soluble sugars. In view of the above-mentioned results, radiation stress led to a UV-B time-dependent dose increase in the activity of two enzymes decomposing carbohydrate: invertase and glucosidase. Our results suggest that the exposure of cucumber plants to supplemental UV-B doses does not limit the availability of the photoassimilate. Carbohydrates are required to provide not only respiratory energy for protection, maintenance (and repair of plant activity and structure, but also provide biosynthetic carbon skeletons for secondary metabolite synthesis

  14. Prognostic Implication of M2 Macrophages Are Determined by the Proportional Balance of Tumor Associated Macrophages and Tumor Infiltrating Lymphocytes in Microsatellite-Unstable Gastric Carcinoma.

    Directory of Open Access Journals (Sweden)

    Kyung-Ju Kim

    Full Text Available Tumor associated macrophages are major inflammatory cells that play an important role in the tumor microenvironment. In this study, we investigated the prognostic significance of tumor associated macrophages (TAMs in MSI-high gastric cancers using immunohistochemistry. CD68 and CD163 were used as markers for total infiltrating macrophages and M2-polarized macrophages, respectively. The density of CD68+ or CD163+ TAMs in four different areas (epithelial and stromal compartments of both the tumor center and invasive front were analyzed in 143 cases of MSI-high advanced gastric cancers using a computerized image analysis system. Gastric cancers were scored as "0" or "1" in each area when the density of CD68+ and CD163+ TAMs was below or above the median value. Low density of CD68+ or CD163+ macrophages in four combined areas was closely associated with more frequent low-grade histology and the intestinal type tumor of the Lauren classification. In survival analysis, the low density of CD163+ TAMs was significantly associated with poor disease-free survival. In multivariate survival analysis, CD163+ TAMs in four combined areas, stromal and epithelial compartments of both tumor center and invasive front were independent prognostic indicator in MSI-high gastric cancers. In addition, the density of CD163+ TAMs correlated with tumor infiltrating lymphocytes (TILs. Our results indicate that the high density of CD163+ TAMs is an independent prognostic marker heralding prolonged disease-free survival and that the prognostic implication of CD163+ TAMs might be determined by the proportional balance of TAMs and TILs in MSI-high gastric cancers.

  15. A combined approach of human leukocyte antigen ligandomics and immunogenicity analysis to improve peptide-based cancer immunotherapy.

    Science.gov (United States)

    Peper, Janet Kerstin; Stevanović, Stefan

    2015-10-01

    The breakthrough development of immune checkpoint inhibitors as clinically effective novel therapies demonstrates the potential of cancer immunotherapy. The identification of suitable targets for specific immunotherapy, however, remains a challenging task. Most peptides previously used for vaccination in clinical trials were able to elicit strong immunological responses but failed with regard to clinical benefit. This might, at least partly, be caused by an inadequate peptide selection, usually derived from established tumor-associated antigens which are not necessarily presented as human leukocyte antigen (HLA) ligands. Recently, HLA ligandome analysis revealed cancer-associated peptides, which have been used in clinical trials showing encouraging impact on survival. To improve peptide-based cancer immunotherapy, our group established a combined approach of HLA ligandomics and immunogenicity analysis for the identification of vaccine peptides. This approach is based on the identification of naturally presented HLA ligands on tumor samples, the selection of tumor-associated/tumor-specific HLA ligands and their subsequent testing for immunogenicity in vitro. In this review, we want to present our pipeline for the identification of vaccine peptides, focusing on ovarian cancer, and want to discuss differences to other approaches. Furthermore, we want to give a short outlook of a potential multi-peptide vaccination trial using the novel identified peptides.

  16. A platform to screen for C-type lectin receptor-binding carbohydrates and their potential for cell-specific targeting and immune modulation.

    Science.gov (United States)

    Maglinao, Maha; Eriksson, Magdalena; Schlegel, Mark K; Zimmermann, Stephanie; Johannssen, Timo; Götze, Sebastian; Seeberger, Peter H; Lepenies, Bernd

    2014-02-10

    Myeloid C-type lectin receptors (CLRs) in innate immunity represent a superfamily of pattern recognition receptors that recognize carbohydrate structures on pathogens and self-antigens. The primary interaction of an antigen-presenting cell and a pathogen shapes the following immune response. Therefore, the identification of CLR ligands that can either enhance or modulate the immune response is of interest. We have developed a screening platform based on glycan arrays to identify immune modulatory carbohydrate ligands of CLRs. A comprehensive library of CLRs was expressed by fusing the extracellular part of each respective CLR, the part containing the carbohydrate-recognition domain (CRD), to the Fc fragment of human IgG1 molecules. CLR-Fc fusion proteins display the CRD in a dimeric form, are properly glycosylated, and can be detected by a secondary antibody with a conjugated fluorophore. Thus, they are valuable tools for high-throughput screening. We were able to identify novel carbohydrate binders of CLRs using the glycan array technology. These CLR-binding carbohydrates were then covalently attached to the model antigen ovalbumin. The ovalbumin neoglycoconjugates were used in a dendritic cell/T cell co-culture assay to stimulate transgenic T cells in vitro. In addition, mice were immunized with these conjugates to analyze the immune modulatory properties of the CLR ligands in vivo. The CLR ligands induced an increased Th1 cytokine production in vitro and modulated the humoral response in vivo. The platform described here allows for the identification of CLR ligands, as well as the evaluation of each ligand's cell-specific targeting and immune modulatory properties.

  17. Swine leukocyte antigen (SLA) diversity in Sinclair and Hanford swine.

    Science.gov (United States)

    Ho, Chak-Sum; Martens, Gregory W; Amoss, Max S; Gomez-Raya, Luis; Beattie, Craig W; Smith, Douglas M

    2010-03-01

    The swine leukocyte antigen (SLA) haplotype B is associated with increased penetrance of the tumor traits in Sinclair swine cutaneous melanoma (SSCM). We established a series of SinclairxHanford swine crosses to facilitate genetic mapping of the tumor-associated loci. In this study, the SLA diversity in the founding animals was characterized for effective selection of maximum tumor penetrance in the pedigrees. Using the sequence-based typing (SBT) method we identified a total of 29 alleles at five polymorphic SLA loci (SLA-1, SLA-3, SLA-2, DRB1 and DQB1) representing six class I and five class II haplotypes. We subsequently developed a rapid PCR-based typing assay using sequence-specific primers (PCR-SSP) to efficiently follow the SLA types of the crossbred progeny. In a total of 469 animals we identified three crossovers within the class I region and three between the class I and class II regions, which corresponded to recombination frequencies of 0.39% and 0.56%, respectively. We also confirmed the presence of two expressed SLA-1 loci in three of the class I haplotypes and were able to determine the relative chromosomal arrangement of the duplicated loci in two haplotypes. This study furthers our understanding of the allelic architecture and polymorphism of the SLA system and will facilitate the mapping of loci associated with the expression of SSCM.

  18. [Antigenic response against PPD and antigen 60 in tubercular patients: single antigen versus the combined test].

    Science.gov (United States)

    Máttar, S; Broquetas, J M; Gea, J; Aran, X; el-Banna, N; Sauleda, J; Torres, J M

    1992-05-01

    We analyze serum samples from 70 patients with pulmonary tuberculosis and 50 healthy individuals. The antigenic activity (IgG) against protein purified antigen (PPD) and antigen 60 (A60) from M. tuberculosis. Thirteen patients were also HIV infected, and three patients had AIDS defined by the presence of disseminated tuberculosis. The test using antigen alone showed a 77% sensitivity and 74% specificity when PPD is used. When A60 was used, both values improved (81% sensitivity, 94% specificity). The use of a combined test (PPD and A60) improves the sensitivity (89%) but reduces the specificity (82%). The HIV infected patients showed similar responses to those of other patients. The combined use of different antigens might be useful for diagnosing tuberculosis. PMID:1390996

  19. Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors

    DEFF Research Database (Denmark)

    Arendrup, M; Hansen, J E; Clausen, H;

    1991-01-01

    not inhibit the HTLV-IIIB/lyB or the HTLV-IIIB/lyO isolate. Specificity of the MAb-mediated inhibition was shown using A-antigen (tetrasaccharide). Thus, HIV infection of PBMC from donors with blood type A appears to induce expression of host-cell-encoded carbohydrate blood group A epitope on HIV which can...

  20. COLONOSCOPY AND CARCINOEMBRYONIC ANTIGEN VARIATIONS

    Directory of Open Access Journals (Sweden)

    Rita G SOUSA

    2014-03-01

    Full Text Available Context Colonoscopy is essential for synchronous and metachronous cancer detection. Carcinoembryonic antigen is a colorectal cancer tumor marker, important as a follow-up tool in patients with previous colorectal cancer. False-positive carcinoembryonic antigen elevation results in multiples exams and in patient anxiety. In literature, there is reference to transient carcinoembryonic antigen increase with colonoscopy. Objective To evaluate the influence of bowel preparation and colonoscopy in carcinoembryonic antigen blood levels. Methods We prospectively studied subjects that underwent routine colonoscopy in our institution. Blood samples were collected (1 before bowel cleaning, (2 before colonoscopy and (3 immediately after colonoscopy. Blood carcinoembryonic antigen levels were determined by “Sandwich” immunoassay. The statistical methods used were the paired t-test and ANOVA. Results Thirty-seven patients (22M/15F were included; age range 28-84 (mean 56 years. Mean carcinoembryonic antigen values were 1.9, 2 and 1.8 for (1, (2 and (3, respectively. An increase in value (2 compared with (1 was observed in 20/37 patients (P = 0.018, mainly in younger patients and in patients requiring more endoluminal interventions. In 29/37 patients, the CEA value decreased from (2 to (3 (P = 1.3x10-7. Conclusions A trend for carcinoembryonic antigen increase after bowel cleaning was observed, especially in younger patients and in patients with more endoluminal interventions, but without clinical meaning.

  1. Carbohydrates/nucleosides/RNA-DNA-ligand interactions

    Energy Technology Data Exchange (ETDEWEB)

    Kaptein, R.; McConnell, B.; Serianni, A.S.; Silks, L.A. III

    1994-12-01

    Carbohydrate and nucleotide structural determination using modern spectroscopic techniques is dependent on our ability to label oligonucleotides and oligosaccharides with stable isotopes. Uniform Carbon 13 and Nitrogen 15 labeling of oligonucleotides is important to present-day efforts, which are focused on determining the structure of relatively small oligosaccharides and oligonucleotides, which form the elements of larger structures. Because of the relatively recent interest in three-dimensional structure, the development of techniques used to label them has lagged behind parallel techniques used to label peptides and proteins. Therefore, this group`s discussion focused primarily on problems faced today in obtaining oligonucleotides labeled uniformly with carbon 13 and nitrogen 15.

  2. Multimodal CARS microscopy of structured carbohydrate biopolymers

    Science.gov (United States)

    Slepkov, Aaron D.; Ridsdale, Andrew; Pegoraro, Adrian F.; Moffatt, Douglas J.; Stolow, Albert

    2010-01-01

    We demonstrate the utility of multimodal coherent anti-Stokes Raman scattering (CARS) microscopy for the study of structured condensed carbohydrate systems. Simultaneous second-harmonic generation (SHG) and spectrally-scanned CARS microscopy was used to elucidate structure, alignment, and density in cellulose cotton fibers and in starch grains undergoing rapid heat-moisture swelling. Our results suggest that CARS response of the O-H stretch region (3000 cm−1–3400 cm−1), together with the commonly-measured C-H stretch (2750 cm−1–2970 cm−1) and SHG provide potentially important structural information and contrast in these materials. PMID:21258555

  3. A high-power carbohydrate fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, Ragnar [SuFuCell AB, Bytaregatan 23, SE 222 21 Lund (Sweden); Folkesson, Boerje [Bronsaaldersvaegen 21, SE-226 54 Lund (Sweden); Spaziante, Placido M. [Cellennium Co., Ltd., 14th Floor Gypsum Metropolitan Tower, 539 Sri Ayudhaya Rd., Bangkok 10400 (Thailand); Veerasai, Waret [Chemistry Department, Faculty of Science, Mahidol University, Bangkok 10400 (Thailand); Exell, Robert H.B. [Joint Graduate School of Energy and Environment, King Mongkut' s University of Technology Thonburi, 91 Prachauthit Rd., Bangmod, Tungkru, Bangkok 10140 (Thailand)

    2006-04-01

    This paper reports the development of a fuel cell consisting of a vanadium flow battery in which the vanadium ions are reduced by sugar (from a carbohydrate) to oxidation state +3 on one side of a membrane, and are oxidized to state +5 on the other side by oxygen. The theoretical upper limit to the conversion efficiency of the energy in sugar by this method under standard conditions is 54%. We have obtained efficiencies up to 45% in our laboratory tests. This way of using biomass for electricity production avoids the Carnot cycle losses in heat engines. (author)

  4. Carbohydrate nanotechnology: hierarchical assembly using nature's other information carrying biopolymers.

    Science.gov (United States)

    Han, Xu; Zheng, Yeting; Munro, Catherine J; Ji, Yiwen; Braunschweig, Adam B

    2015-08-01

    Despite their central role in directing some of the most complex biological processes, carbohydrates--nature's other information carrying biopolymer--have been largely ignored as building blocks for synthetic hierarchical assemblies. The non-stoichiometric binding and astronomical diversity characteristic of carbohydrates could lead to tantalizingly complex assembly algorithms, but these attributes simultaneously increase the difficulty of preparing carbohydrate assemblies and anticipating their behavior. Convergences in biotechnology, nanotechnology, polymer chemistry, surface science, and supramolecular chemistry have led to many recent important breakthroughs in glycan microarrays and synthetic carbohydrate receptors, where the idiosyncrasies of carbohydrate structure and binding are increasingly considered. We hope to inspire more researchers to consider carbohydrate structure, diversity, and binding as attractive tools for constructing synthetic hierarchical assemblies.

  5. Carbohydrate-active enzymes from pigmented Bacilli: a genomic approach to assess carbohydrate utilization and degradation

    Directory of Open Access Journals (Sweden)

    Henrissat Bernard

    2011-09-01

    Full Text Available Abstract Background Spore-forming Bacilli are Gram-positive bacteria commonly found in a variety of natural habitats, including soil, water and the gastro-intestinal (GI-tract of animals. Isolates of various Bacillus species produce pigments, mostly carotenoids, with a putative protective role against UV irradiation and oxygen-reactive forms. Results We report the annotation of carbohydrate active enzymes (CAZymes of two pigmented Bacilli isolated from the human GI-tract and belonging to the Bacillus indicus and B. firmus species. A high number of glycoside hydrolases (GHs and carbohydrate binding modules (CBMs were found in both isolates. A detailed analysis of CAZyme families, was performed and supported by growth data. Carbohydrates able to support growth as the sole carbon source negatively effected carotenoid formation in rich medium, suggesting that a catabolite repression-like mechanism controls carotenoid biosynthesis in both Bacilli. Experimental results on biofilm formation confirmed genomic data on the potentials of B. indicus HU36 to produce a levan-based biofilm, while mucin-binding and -degradation experiments supported genomic data suggesting the ability of both Bacilli to degrade mammalian glycans. Conclusions CAZy analyses of the genomes of the two pigmented Bacilli, compared to other Bacillus species and validated by experimental data on carbohydrate utilization, biofilm formation and mucin degradation, suggests that the two pigmented Bacilli are adapted to the intestinal environment and are suited to grow in and colonize the human gut.

  6. CARBOHYDRATE INGESTION AND EXERCISE: EFFECTS ON METABOLISM AND PERFORMANCE

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@KEY POINTS ■ Carbohydrate is the preferred fuel for most competitive sports;an inadequate supply of carbohydrate in the body often leads to poor performance. ■ Carbohydrate ingestion during exercise increases blood glucose availability and maintains the ability of the body to use carbohydrate as fuel during exercise.When carbohydrate is consumed during exercise,glucose uptake by muscles is increased,and the breakdown of glycogen in the liver into blood glucose is reduced,thus saving liver glycogen until late in exercise.The use of muscle glycogen for energy is generally unaffected by carbohydrate feeding.However,during prolonged running,the breakdown of muscle glycogen may be slowed because the supply of blood glucose is improved when carbohydrate is consumed.These metabolic responses underlie the performance benefit that accompanies carbohydrate ingestion during exercise. ■ There are some minor differences among glucose,sucrose,and maltodextrins in their effects on metabolism,but each of them can enhance performance when ingested in the appropriate quantity during exercise.Fructose alone is not an effective carbohydrate supplement because of its slow absorption and slow conversion by the body to glucose,but when small amounts of fructose are combined with other carbohydrates,fructose can be beneficial. ■ Ingesting carbohydrate at a rate of 30-60 grams per hour can improve exercise erformance.A good way to achieve this carbohydrate intake is to consume 600-to-1200 ml(20-to-40 oz)of a sports drink during each hour of exercise.Consuming carbohydrate in a beverage provides an added benefit of preventing potentially harmful effects of dehydration on performance.

  7. Synthesis and evaluation of novel carbocyclic carbohydrate analogues

    OpenAIRE

    Adamson, Christopher William

    2016-01-01

    Carbohydrate analogues play an indispensible role in the study of glycan processing enzymes. These compounds have attracted attention as probes of enzyme mechanisms, as chemical tools for the elucidation of enzyme function and as potential pharmaceuticals. The development of organocatalytic aldol chemistry has fundamentally altered the way chemists approach the synthesis of carbohydrate analogues. In this thesis I highlight a novel strategy toward the synthesis of carbocyclic carbohydrate ana...

  8. The least-cost low-carbohydrate diet is expensive.

    Science.gov (United States)

    Raffensperger, John F

    2008-01-01

    This article describes the use of operations research methods to study the minimum possible cost of a low-carbohydrate diet. The study compares this cost to the minimum cost of a diet with no limitation on carbohydrate. The rationale for this study is the popularity of the low-carbohydrate diets and their perceived high cost. The method used was an operations research approach to find a set of least cost diets, varying the required carbohydrate. This method was chosen to avoid potential concerns with real diets that may be nutritionally deficient or could be had for a lower cost. The major finding is that the cheapest possible low-carbohydrate diet costs about triple the cost of the cheapest diet with no constraint on carbohydrate. Furthermore, the minimum cost of a diet low in both carbohydrate and fat is 5 to 10 times the cost of the cheapest diet, depending on the relative amounts of these nutrients. As carbohydrate and fat are constrained, cost increases dramatically and nonlinearly. The study identifies which nutrients had the greatest effect on cost for a low-carbohydrate and low-fat diet.

  9. Renewable Hydrogen Carrier — Carbohydrate: Constructing the Carbon-Neutral Carbohydrate Economy

    Directory of Open Access Journals (Sweden)

    Y.-H. Percival Zhang

    2011-01-01

    Full Text Available The hydrogen economy presents an appealing energy future but its implementation must solve numerous problems ranging from low-cost sustainable production, high-density storage, costly infrastructure, to eliminating safety concern. The use of renewable carbohydrate as a high-density hydrogen carrier and energy source for hydrogen production is possible due to emerging cell-free synthetic biology technology—cell-free synthetic pathway biotransformation (SyPaB. Assembly of numerous enzymes and co-enzymes in vitro can create complicated set of biological reactions or pathways that microorganisms or catalysts cannot complete, for example, C6H10O5 (aq + 7 H2O (l à 12 H2 (g + 6 CO2 (g (PLoS One 2007, 2:e456. Thanks to 100% selectivity of enzymes, modest reaction conditions, and high-purity of generated hydrogen, carbohydrate is a promising hydrogen carrier for end users. Gravimetric density of carbohydrate is 14.8 H2 mass% if water can be recycled from proton exchange membrane fuel cells or 8.33% H2 mass% without water recycling. Renewable carbohydrate can be isolated from plant biomass or would be produced from a combination of solar electricity/hydrogen and carbon dioxide fixation mediated by high-efficiency artificial photosynthesis mediated by SyPaB. The construction of this carbon-neutral carbohydrate economy would address numerous sustainability challenges, such as electricity and hydrogen storage, CO2 fixation and long-term storage, water conservation, transportation fuel production, plus feed and food production.

  10. CARBOHYDRATE INTAKE CONSIDERATIONS FOR YOUNG ATHLETES

    Directory of Open Access Journals (Sweden)

    Veronica Montfort-Steiger

    2007-09-01

    Full Text Available Good nutritional practices are important for exercise performance and health during all ages. Athletes and especially growing children engaged in heavy training have higher energy and nutrient requirements compared to their non-active counterparts. Scientific understanding of sports nutrition for the young athlete is lacking behind the growing number of young athletes engaged in sports. Most of the sports nutrition recommendations given to athletic children and adolescents are based on adult findings due to the deficiency in age specific information in young athletes. Therefore, this review reflects on child specific sports nutrition, particularly on carbohydrate intake and metabolism that distinguishes the child athlete from the adult athlete. Children are characterised to be in an insulin resistance stage during certain periods of maturation, have different glycolytic/metabolic responses during exercise, have a tendency for higher fat oxidation during exercise and show different heat dissipation mechanisms compared to adults. These features point out that young athletes may need different nutritional advice on carbohydrate for exercise to those from adult athletes. Sport drinks for example may need to be adapted to children specific needs. However, more research in this area is warranted to clarify sports nutrition needs of the young athlete to provide better and healthy nutritional guidance to young athletes

  11. Impact of dietary polyphenols on carbohydrate metabolism.

    Science.gov (United States)

    Hanhineva, Kati; Törrönen, Riitta; Bondia-Pons, Isabel; Pekkinen, Jenna; Kolehmainen, Marjukka; Mykkänen, Hannu; Poutanen, Kaisa

    2010-03-31

    Polyphenols, including flavonoids, phenolic acids, proanthocyanidins and resveratrol, are a large and heterogeneous group of phytochemicals in plant-based foods, such as tea, coffee, wine, cocoa, cereal grains, soy, fruits and berries. Growing evidence indicates that various dietary polyphenols may influence carbohydrate metabolism at many levels. In animal models and a limited number of human studies carried out so far, polyphenols and foods or beverages rich in polyphenols have attenuated postprandial glycemic responses and fasting hyperglycemia, and improved acute insulin secretion and insulin sensitivity. The possible mechanisms include inhibition of carbohydrate digestion and glucose absorption in the intestine, stimulation of insulin secretion from the pancreatic beta-cells, modulation of glucose release from the liver, activation of insulin receptors and glucose uptake in the insulin-sensitive tissues, and modulation of intracellular signalling pathways and gene expression. The positive effects of polyphenols on glucose homeostasis observed in a large number of in vitro and animal models are supported by epidemiological evidence on polyphenol-rich diets. To confirm the implications of polyphenol consumption for prevention of insulin resistance, metabolic syndrome and eventually type 2 diabetes, human trials with well-defined diets, controlled study designs and clinically relevant end-points together with holistic approaches e.g., systems biology profiling technologies are needed.

  12. Impact of Dietary Polyphenols on Carbohydrate Metabolism

    Directory of Open Access Journals (Sweden)

    Kati Hanhineva

    2010-03-01

    Full Text Available Polyphenols, including flavonoids, phenolic acids, proanthocyanidins and resveratrol, are a large and heterogeneous group of phytochemicals in plant-based foods, such as tea, coffee, wine, cocoa, cereal grains, soy, fruits and berries. Growing evidence indicates that various dietary polyphenols may influence carbohydrate metabolism at many levels. In animal models and a limited number of human studies carried out so far, polyphenols and foods or beverages rich in polyphenols have attenuated postprandial glycemic responses and fasting hyperglycemia, and improved acute insulin secretion and insulin sensitivity. The possible mechanisms include inhibition of carbohydrate digestion and glucose absorption in the intestine, stimulation of insulin secretion from the pancreatic b-cells, modulation of glucose release from the liver, activation of insulin receptors and glucose uptake in the insulin-sensitive tissues, and modulation of intracellular signalling pathways and gene expression. The positive effects of polyphenols on glucose homeostasis observed in a large number of in vitro and animal models are supported by epidemiological evidence on polyphenol-rich diets. To confirm the implications of polyphenol consumption for prevention of insulin resistance, metabolic syndrome and eventually type 2 diabetes, human trials with well-defined diets, controlled study designs and clinically relevant end-points together with holistic approaches e.g., systems biology profiling technologies are needed.

  13. Radiolabeled Peptide Scaffolds for PET/SPECT - Optical in Vivo Imaging of Carbohydrate-Lectin Interactions

    Energy Technology Data Exchange (ETDEWEB)

    Deutscher, Susan

    2014-09-30

    The objective of this research is to develop phage display-selected peptides into radio- and fluoresecently- labeled scaffolds for the multimodal imaging of carbohydrate-lectin interactions. While numerous protein and receptor systems are being explored for the development of targeted imaging agents, the targeting and analysis of carbohydrate-lectin complexes in vivo remains relatively unexplored. Antibodies, nanoparticles, and peptides are being developed that target carbohydrate-lectin complexes in living systems. However, antibodies and nanoparticles often suffer from slow clearance and toxicity problems. Peptides are attractive alternative vehicles for the specific delivery of radionuclides or fluorophores to sites of interest in vivo, although, because of their size, uptake and retention may be less than antibodies. We have selected high affinity peptides that bind a specific carbohydrate-lectin complex involved in cell-cell adhesion and cross-linking using bacteriophage (phage) display technologies (1,2). These peptides have allowed us to probe the role of these antigens in cell adhesion. Fluorescent versions of the peptides have been developed for optical imaging and radiolabeled versions have been used in single photon emission computed tomography (SPECT) and positron emission tomography (PET) in vivo imaging (3-6). A benefit in employing the radiolabeled peptides in SPECT and PET is that these imaging modalities are widely used in living systems and offer deep tissue sensitivity. Radiolabeled peptides, however, often exhibit poor stability and high kidney uptake in vivo. Conversely, optical imaging is sensitive and offers good spatial resolution, but is not useful for deep tissue penetration and is semi-quantitative. Thus, multimodality imaging that relies on the strengths of both radio- and optical- imaging is a current focus for development of new in vivo imaging agents. We propose a novel means to improve the efficacy of radiolabeled and fluorescently

  14. Small-angle neutron scattering study of recombinant yeast-derived human hepatitis B virus surface antigen vaccine particle

    Science.gov (United States)

    Sato, M.; Ito, Y.; Kameyama, K.; Imai, M.; Ishikawa, N.; Takagi, T.

    1995-02-01

    The overall and internal structure of recombinant yeast-derived human hepatitis B virus surface antigen vaccine particles was investigated by small-angle neutron scattering using the contrast variation method. The vaccine is a nearly spherical particle, and its contrast-matching point was determined to be at about 24% D 2O content, indicating that a large part of the vaccine particle is occupied by lipids and carbohydrates from the yeast. The Stuhrmann plot suggests that the surface antigens exist predominantly in the peripheral region of the particle, which is favorable to the induction of anti-virus antibodies.

  15. Acute Effects of Carbohydrate Supplementation on Intermittent Sports Performance

    Directory of Open Access Journals (Sweden)

    Lindsay B. Baker

    2015-07-01

    Full Text Available Intermittent sports (e.g., team sports are diverse in their rules and regulations but similar in the pattern of play; that is, intermittent high-intensity movements and the execution of sport-specific skills over a prolonged period of time (~1–2 h. Performance during intermittent sports is dependent upon a combination of anaerobic and aerobic energy systems, both of which rely on muscle glycogen and/or blood glucose as an important substrate for energy production. The aims of this paper are to review: (1 potential biological mechanisms by which carbohydrate may impact intermittent sport performance; (2 the acute effects of carbohydrate ingestion on intermittent sport performance, including intermittent high-intensity exercise capacity, sprinting, jumping, skill, change of direction speed, and cognition; and (3 what recommendations can be derived for carbohydrate intake before/during exercise in intermittent sports based on the available evidence. The most researched intermittent sport is soccer but some sport-specific studies have also been conducted in other sports (e.g., rugby, field hockey, basketball, American football, and racquet sports. Carbohydrate ingestion before/during exercise has been shown in most studies to enhance intermittent high-intensity exercise capacity. However, studies have shown mixed results with regards to the acute effects of carbohydrate intake on sprinting, jumping, skill, change of direction speed, and cognition. In most of these studies the amount of carbohydrate consumed was ~30–60 g/h in the form of a 6%–7% carbohydrate solution comprised of sucrose, glucose, and/or maltodextrin. The magnitude of the impact that carbohydrate ingestion has on intermittent sport performance is likely dependent on the carbohydrate status of the individual; that is, carbohydrate ingestion has the greatest impact on performance under circumstances eliciting fatigue and/or hypoglycemia. Accordingly, carbohydrate ingestion before

  16. Cognitive awareness of carbohydrate intake does not alter exercise‐induced lymphocyte apoptosis

    OpenAIRE

    James Wilfred Navalta; Brian Keith McFarlin; Scott Lyons; Scott Wesley Arnett; Mark Anthony Schafer

    2011-01-01

    OBJECTIVE: The purpose of this investigation was to determine whether cognitive awareness of carbohydrate beverage consumption affects exercise‐induced lymphocyte apoptosis, independent of actual carbohydrate intake. INTRODUCTION: Carbohydrate supplementation during aerobic exercise generally protects against the immunosuppressive effects of exercise. It is not currently known whether carbohydrate consumption or simply the knowledge of carbohydrate consumption also has that effect. METHODS: E...

  17. BIOCHEMICAL AND IMMUNOLOGICAL CHARACTERIZATION OF THE 200kD SCHISTOSOMULUM SURFACE ANTIGEN COMMON TO SCHISTOSOMA MANSONI AND SCHISTOSOMA JAPONICUM%曼氏和日本血吸虫童虫体表200kD共同抗原的生化与免疫学特性

    Institute of Scientific and Technical Information of China (English)

    易新元; 周金春; 王庆林

    2000-01-01

    Objective To study the biochemecal and immunological characterization of the 200 kD schistosomulum surface antigen Method and results A very high molecular weight schistosomulum surface antigen of Mr>200kD was identified and characterized using monoclonal antibodies. Carbohydrate modification experiments followed by radioimmunobinding assays demonstrated that the epitope recognised by the mAbs on this antigen was carbohydrate in nature, while protein digestion experiments followed by SDS-PAGE indicated that this antigen also contained protein. Immunoprecipitation of 125I-labelled cercarial, schistosomulum, adult worm and miracidial surface antigens followed by gel analysis showed the carbohydrate epitope to be present on 5 cercarial, 2 schistosomulum and 5 miracidial surface molecules, and suggested a possible ecological function involved in adapting the parasite to the aquatic free-living stages of its life cycle and possibly also in protecting the early schistosomula from host immune damage. The 5 cercarial surfacs antigens proved to be associated with the CHR, since all the mAbs which recognised those antigens could induce a strong CHR. A kinetic investigation of the carbohydrate epitope on schistosomula of different ages demonstrated a gradual and possibly irreversible loss during the culture period. The epitope completely disappeared from the surface of adult worms. Conclusion To demonstrate an epitope common to a number of surface molecules of various developmental stages of schistosome and therefore explains the immunological cross - reactivity among different stages at the molecular level.

  18. Potential of carbohydrate-binding agents as therapeutics against enveloped viruses.

    Science.gov (United States)

    François, K O; Balzarini, J

    2012-03-01

    Twenty-seven years after the discovery of HIV as the cause of AIDS more than 25 drugs directed against four different viral targets (i.e. reverse transcriptase, protease, integrase, envelope gp41) and one cellular target (i.e. CCR5 co-receptor) are available for treatment. However, the search for an efficient vaccine is still ongoing. One of the main problems is the presence of a continuously evolving dense carbohydrate shield, consisting of N-linked glycans that surrounds the virion and protects it against efficient recognition and persistent neutralization by the immune system. However, several lectins from the innate immune system specifically bind to these glycans in an attempt to process the virus antigens to provoke an immune response. Across a wide variety of different species in nature lectins can be found that can interact with the glycosylated envelope of HIV-1 and can block the infection of susceptible cells by the virus. In this review, we will give an overview of the lectins from non-mammalian origin that are endowed with antiviral properties and discuss the complex interactions between lectins of the innate immune system and HIV-1. Also, attention will be given to different carbohydrate-related modalities that can be exploited for antiviral chemotherapy.

  19. Amido/ureidosubstituted benzenesulfonamides-isatin conjugates as low nanomolar/subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform XII.

    Science.gov (United States)

    Eldehna, Wagdy M; Fares, Mohamed; Ceruso, Mariangela; Ghabbour, Hazem A; Abou-Seri, Sahar M; Abdel-Aziz, Hatem A; Abou El Ella, Dalal A; Supuran, Claudiu T

    2016-03-01

    By using a molecular hybridization approach, two series of amido/ureidosubstituted benzenesulfonamides incorporating substituted-isatin moieties were synthesized. The prepared derivatives were in vitro evaluated for their inhibitory activity against human carbonic anhydrase (hCA, EC 4.2.1.1) I, II (cytosolic) and IX, XII (transmembrane, tumor-associated) isoforms. All these isoforms were inhibited in variable degrees by the sulfonamides reported here. hCA I was inhibited with KIs in the range of 7.9-894 nM, hCA II in the range of 7.5-1645 nM (with one compound having a KI > 10 μM); hCA IX in the range of 5.0-240 nM, whereas hCA XII in the range of 0.47-2.83 nM. As all these isoforms are involved in various pathologies, in which their inhibition can be exploited therapeutically, the derivatives reported here may represent interesting extensions to the field of CA inhibitors of the sulfonamide type. PMID:26840366

  20. Noble metal nanoparticle-induced oxidative stress modulates tumor associated macrophages (TAMs) from an M2 to M1 phenotype: An in vitro approach.

    Science.gov (United States)

    Pal, Ramkrishna; Chakraborty, Biswajit; Nath, Anupam; Singh, Leichombam Mohindro; Ali, Mohammed; Rahman, Dewan Shahidur; Ghosh, Sujit Kumar; Basu, Abhishek; Bhattacharya, Sudin; Baral, Rathindranath; Sengupta, Mahuya

    2016-09-01

    Diagnosis of cancer and photothermal therapy using optoelectronic properties of noble metal nanoparticles (NPs) has established a new therapeutic approach for treating cancer. Here we address the intrinsic properties of noble metal NPs (gold and silver) as well as the mechanism of their potential antitumor activity. For this, the study addresses the functional characterization of tumor associated macrophages (TAMs) isolated from murine fibrosarcoma induced by a chemical carcinogen, 3-methylcholanthrene (MCA). We have previously shown antitumor activity of both gold nanoparticles (AuNPs) and silver nanoparticle (AgNPs) in vivo in a murine fibrosarcoma model. In the present study, it has been seen that AuNPs and AgNPs modulate the reactive oxygen species (ROS) and reactive nitrogen species (RNS) production, suppressing the antioxidant system of cells (TAMs). Moreover, the antioxidant-mimetic action of these NPs maintain the ROS and RNS levels in TAMs which act as second messengers to activate the proinflammatory signaling cascades. Thus, while there is a downregulation of tumor necrosis factor-α (TNF-α) and Interleukin-10 (IL-10) in the TAMs, the proinflammatory cytokine Interleukin-12 (IL-12) is upregulated resulting in a polarization of TAMs from M2 (anti-inflammatory) to M1 (pro-inflammatory) nature. PMID:27344639

  1. A Novel Strategy for Inducing the Antitumor Effects of Triterpenoid Compounds: Blocking the Protumoral Functions of Tumor-Associated Macrophages via STAT3 Inhibition

    Directory of Open Access Journals (Sweden)

    Yukio Fujiwara

    2014-01-01

    Full Text Available There are many types of nontumor cells, including leukocytes, fibroblasts, and endothelial cells, in the tumor microenvironment. Among these cells, infiltrating macrophages have recently received attention as novel target cells due to their protumoral functions. Infiltrating macrophages are called tumor-associated macrophages (TAMs. TAMs polarized to the M2 phenotype are involved in tumor development and are associated with a poor clinical prognosis. Therefore, the regulation of TAM activation or M2 polarization is a new strategy for antitumor therapy. We screened natural compounds possessing an inhibitory effect on the M2 polarization of human macrophages. Among 200 purified natural compounds examined, corosolic acid (CA and oleanolic acid (OA, both are categorized in triterpenoid compounds, inhibited macrophage polarization to M2 phenotype by suppressing STAT3 activation. CA and OA also directly inhibited tumor cell proliferation and sensitized tumor cells to anticancer drugs, such as adriamycin and cisplatin. The in vivo experiments showed that CA significantly suppressed subcutaneous tumor development and lung metastasis in a murine sarcoma model. The application of triterpenoid compounds, such as CA and OA, is a potential new anticancer therapy targeting macrophage activation, with synergistic effects with anticancer agents.

  2. In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities.

    Directory of Open Access Journals (Sweden)

    Oscar M Pello

    Full Text Available Although tumor-associated macrophages (TAMs are involved in tumor growth and metastasis, the mechanisms controlling their pro-tumoral activities remain largely unknown. The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macrophages infiltrating human tumors. In this study, we exploited the predominant expression of LysM in myeloid cells to generate c-Myc(fl/fl LysM(cre/+ mice, which lack c-Myc in macrophages, to investigate the role of macrophage c-MYC expression in cancer. Under steady-state conditions, immune system parameters in c-Myc(fl/fl LysM(cre/+ mice appeared normal, including the abundance of different subsets of bone marrow hematopoietic stem cells, precursors and circulating cells, macrophage density, and immune organ structure. In a model of melanoma, however, TAMs lacking c-Myc displayed a delay in maturation and showed an attenuation of pro-tumoral functions (e.g., reduced expression of VEGF, MMP9, and HIF1α that was associated with impaired tissue remodeling and angiogenesis and limited tumor growth in c-Myc(fl/fl LysM(cre/+ mice. Macrophage c-Myc deletion also diminished fibrosarcoma growth. These data identify c-Myc as a positive regulator of the pro-tumoral program of TAMs and suggest c-Myc inactivation as an attractive target for anti-cancer therapy.

  3. Signiifcance of Serum Tumor-Associated Material andβ2-microglobulin Detection in Patients with Non-Hodgkin’s Lymphoma

    Institute of Scientific and Technical Information of China (English)

    Li Xiaoyou; Feng Jifeng; Wu Jianqiu; Tang Weiyan; Liu Yufei; Zhang Yan

    2014-01-01

    Objective: To explore the clinical significance of tumor associated material (TAM) and β2-microglobulin (β2-MG) in the diagnosis and evaluation of chemotherapeutic efifcacy in patients with non-Hodgkin’s lymphoma (NHL). Methods:A total of 161 patients with NHL and another 37 examined healthy people were selected to detect their serum TAM and β2-MG levels and analyze the relationship between TAM and β2-MG with NHL progression and prognosis. Results:Serum TAM and β2-MG levels in NHL patients were higher than in healthy people (P0.05), but were lower in patients with indolent lymphoma than in those with invasive and high-invasive lymphoma (P0.05), which decreased evidently after treatment than treatment before (P<0.05). Conclusion:The levels of serum TAM and β2-MG expression in patients with NHL have a certain guiding signiifcance for clinical staging, pathological malignant severity and tumor invasive severity, and detection of TAM and β2-MG has a certain value in diagnosing the therapeutic responses to NHL, able to be an effective index for the diagnosis and efifcacy evaluation in patients with NHL.

  4. Tumor-associated macrophages in immune microenvironment of lung cancer%肺癌免疫微环境中的肿瘤相关巨噬细胞

    Institute of Scientific and Technical Information of China (English)

    丁怡慧; 张锴; 胡悦; 刘莉

    2014-01-01

    With the research on tumor immunity and tumor immunosuppression development,immunotherapies for lung cancer has become a research hotspot.Tumor immune microenvironment plays an important role in tumor genesis,development and metastasis of lung cancer.Tumor-associated macrophages (TAMs) are the dominant leukocyte population found in immune microenvironment of lung cancer.The relationship between TAMs and lung cancer becomes clear with further research.TAMs may become the new target of lung cancer immunotherapy.%随着对肿瘤免疫发生和免疫耐受认识的不断深入,肺癌免疫治疗成为研究的热点.肿瘤免疫微环境在肺癌的发生、发展、转移过程中起着重要作用.肿瘤相关巨噬细胞(TAM)是肺癌免疫微环境中白细胞的主要成分之一,TAM和肺癌的关系随着研究的深入而逐渐明确,TAM作为肺癌免疫治疗新的靶点成为可能.

  5. NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of esophageal cancer regulates the survival and migration of tumor-associated macrophages and cancer cells.

    Science.gov (United States)

    Takase, Nobuhisa; Koma, Yu-Ichiro; Urakawa, Naoki; Nishio, Mari; Arai, Noriaki; Akiyama, Hiroaki; Shigeoka, Manabu; Kakeji, Yoshihiro; Yokozaki, Hiroshi

    2016-09-28

    Tumor-associated macrophages (TAMs) have important roles in the angiogenesis and tumor immunosuppression of various cancers, including esophageal squamous cell carcinomas (ESCCs). To elucidate the roles of TAMs in ESCCs, we compared the gene expression profiles between human peripheral blood monocyte-derived macrophage-like cells (Macrophage_Ls) and Macrophage_Ls stimulated with conditioned medium of the TE series human ESCC cell line (TECM) (TAM_Ls) using cDNA microarray analysis. Among the highly expressed genes in TAM_Ls, we focused on neural cell adhesion molecule (NCAM). NCAM knockdown in TAM_Ls revealed a significant decrease of migration and survival via a suppression of PI3K-Akt and fibroblast growth factor receptor 1 (FGFR1) signaling. Stimulation by TECM up-regulated the level of FGFR1 in Macrophage_Ls. Recombinant human fibroblast growth factor-2 (rhFGF-2) promoted the migration and survival of TAM_Ls and TE-cells through FGFR1 signaling. Our immunohistochemical analysis of 70 surgically resected ESCC samples revealed that the up-regulated FGF-2 in stromal cells, including macrophages, was associated with more aggressive phenotypes and a high number of infiltrating M2 macrophages. These findings may indicate a novel role of NCAM- and FGF-2-mediated FGFR1 signaling in the tumor microenvironment of ESCCs. PMID:27317650

  6. Prognostic impact of tumor-associated macrophage infiltration in non-small cell lung cancer: A systemic review and meta-analysis

    Science.gov (United States)

    Guo, Chenglin; Pu, Qiang; Ma, Lin; Liu, Chengwu; Lin, Feng; Liao, Hu; You, Zongbing; Liu, Lunxu

    2016-01-01

    Tumor-associated macrophages (TAMs) are important components of cancer microenvironment. In the present study, we searched PubMed, Embase, Cochrane library and Web of Science to perform a meta-analysis of 20 studies including a total of 2,572 non-small cell lung cancer (NSCLC) patients, in order to determine the association between TAMs and NSCLC prognosis. The combined hazard ratio (HR) of 9 studies showed that the density of total CD68+ TAMs in the tumor islet and stroma was not associated with overall survival (OS) of the patients. However, the pooled HR of 4 studies showed that high density of CD68+ TAMs in the tumor islet predicted better OS, while the pooled HR of 6 studies showed that high density of CD68+ TAMs in the tumor stroma was associated with poor OS. A high islet/stroma ratio of CD68+ TAMs was associated with better OS. A high density of M1 TAMs in the tumor islet was associated with better OS, while a high density of M2 TAMs in the tumor stroma predicted poor OS. These findings suggest that, although the density of total CD68+ TAMs is not associated with OS, the localization and M1/M2 polarization of TAMs are potential prognostic predictors of NSCLC. PMID:27144518

  7. Hydrazinocurcumin Encapsuled nanoparticles "re-educate" tumor-associated macrophages and exhibit anti-tumor effects on breast cancer following STAT3 suppression.

    Directory of Open Access Journals (Sweden)

    Xiwen Zhang

    Full Text Available Tumor-associated macrophages (TAMs are essential cellular components within tumor microenvironment (TME. TAMs are educated by TME to transform to M2 polarized population, showing a M2-like phenotype, IL-10(high, IL-12(low, TGF-β(high. STAT3 signaling triggers crosstalk between tumor cells and TAMs, and is crucial for the regulation of malignant progression. In our study, legumain-targeting liposomal nanoparticles (NPs encapsulating HC were employed to suppress STAT3 activity and "re-educate" TAMs, and to investigate the effects of suppression of tumor progression in vivo. The results showed that TAMs treated by HC encapsuled NPs could switch to M1-like phenotype, IL-10(low, IL-12(high, TGF-β(low, and the "re-educated" macrophages (M1-like macrophages considerably demonstrated opposite effect of M2-like macrophages, especially the induction of 4T1 cells migration and invasion in vitro, and suppression of tumor growth, angiogenesis and metastasis in vivo. These data indicated that inhibition of STAT3 activity of TAMs by HC-NPs was able to reverse their phenotype and could regulate their crosstalk between tumor cells and TAMs in order to suppress tumor progression.

  8. Whole tumor antigen vaccination using dendritic cells: Comparison of RNA electroporation and pulsing with UV-irradiated tumor cells

    Directory of Open Access Journals (Sweden)

    Benencia Fabian

    2008-04-01

    Full Text Available Abstract Because of the lack of full characterization of tumor associated antigens for solid tumors, whole antigen use is a convenient approach to tumor vaccination. Tumor RNA and apoptotic tumor cells have been used as a source of whole tumor antigen to prepare dendritic cell (DC based tumor vaccines, but their efficacy has not been directly compared. Here we compare directly RNA electroporation and pulsing of DCs with whole tumor cells killed by ultraviolet (UV B radiation using a convenient tumor model expressing human papilloma virus (HPV E6 and E7 oncogenes. Although both approaches led to DCs presenting tumor antigen, electroporation with tumor cell total RNA induced a significantly higher frequency of tumor-reactive IFN-gamma secreting T cells, and E7-specific CD8+ lymphocytes compared to pulsing with UV-irradiated tumor cells. DCs electroporated with tumor cell RNA induced a larger tumor infiltration by T cells and produced a significantly stronger delay in tumor growth compared to DCs pulsed with UV-irradiated tumor cells. We conclude that electroporation with whole tumor cell RNA and pulsing with UV-irradiated tumor cells are both effective in eliciting antitumor immune response, but RNA electroporation results in more potent tumor vaccination under the examined experimental conditions.

  9. Using structure to inform carbohydrate binding module function

    NARCIS (Netherlands)

    Abbott, D. Wade; Lammerts van Bueren, Alicia

    2014-01-01

    Generally, non-catalytic carbohydrate binding module (CBM) specificity has been shown to parallel the catalytic activity of the carbohydrate active enzyme (CAZyme) module it is appended to. With the rapid expansion in metagenomic sequence space for the potential discovery of new CBMs in addition to

  10. Frankincense tapping reduces the carbohydrate storage of Boswellia trees

    NARCIS (Netherlands)

    Mengistu, T.; Sterck, F.J.; Fetene, M.; Bongers, F.

    2013-01-01

    Carbohydrates fixed by photosynthesis are stored in plant organs in the form of starch or sugars. Starch and sugars sum to the total non-structural carbohydrate pool (TNC) and may serve as intermediate pools between assimilation and utilization. We examined the impact of tapping on TNC concentration

  11. Chemical Changes in Carbohydrates Produced by Thermal Processing.

    Science.gov (United States)

    Hoseney, R. Carl

    1984-01-01

    Discusses chemical changes that occur in the carbohydrates found in food products when these products are subjected to thermal processing. Topics considered include browning reactions, starch found in food systems, hydrolysis of carbohydrates, extrusion cooking, processing of cookies and candies, and alterations in gums. (JN)

  12. Influence of dietary carbohydrate level on endocrine status and hepatic carbohydrate metabolism in the marine fish Sparus sarba.

    Science.gov (United States)

    Leung, L Y; Woo, Norman Y S

    2012-04-01

    Silver sea bream, Sparus sarba, were fed two diets of different carbohydrate levels (2 and 20% dextrin) for 4 weeks, and the effects on organ indices, liver composition, serum metabolite and hormone levels and gene expression profile of key enzymes of carbohydrate metabolism in the liver were investigated. By using real-time PCR, mRNA expression levels of carbohydrate metabolic enzymes including glucokinase (GK, glycolysis), glucose-6-phosphatase (G6Pase, gluconeogenesis), glycogen synthase (GS, glycogenesis), glycogen phosphorylase (GP, glycogenolysis) and glucose-6-phosphate dehydrogenase (G6PDH, pentose phosphate pathway) in liver of sea bream have been examined, and it was found that high dietary carbohydrate level increased mRNA level of GK but decreased mRNA levels of G6Pase and GP. However, mRNA levels of GS and G6PDH were not significantly influenced by dietary carbohydrate. Silver sea bream fed high dietary carbohydrate had higher hepatosomatic index (HSI), liver glycogen and protein, but there were no significant changes in gonadosomatic index (GSI), serum glucose and protein level, as well as liver lipid and moisture level. Pituitary growth hormone (GH) and hepatic insulin-like growth factor I (IGF-I) transcript abundance were assayed by real-time PCR, and it was found that both parameters remained unchanged in fish fed different dietary carbohydrate levels. Serum triiodothyronine (T(3)) and thyroxine (T(4)) were not significantly affected by dietary carbohydrate levels, but lower serum cortisol level was found in fish fed high dietary carbohydrate level. These results suggest that silver sea bream is able to adapt to a diet with high carbohydrate content (up to 20% dextrin), the consumption of which would lead to fundamental re-organization of carbohydrate metabolism resulting in hepatic glycogen deposition.

  13. Carbohydrate loading in the preoperative setting.

    Science.gov (United States)

    Hill, L T; Miller, M G A

    2015-03-01

    Nutrition support is an evolving field, and modern clinical nutrition practice should actively incorporate strategies to enhance various clinical outcomes. In surgical patients, clinical benefits can be maximised by nutritional support protocols that minimise and manage the perioperative fasting period. This approach, which includes the perioperative provision of clear carbohydrate-containing fluids, has been shown to be safe, is evidence based, and is supported by many professional societies. Such a strategy has been shown to aid the anaesthetic process and maintain an optimal metabolic state, including improved insulin sensitivity and blunted muscle catabolic activity. Some important consequences of this improved metabolic control include shorter hospital stay and fewer postoperative complications. A proactive multidisciplinary team approach is essential to use this nutrition support strategy with success across a hospital's surgical service. PMID:26294840

  14. Arabinogalactan proteins: focus on carbohydrate active enzymes

    Directory of Open Access Journals (Sweden)

    Eva eKnoch

    2014-06-01

    Full Text Available Arabinogalactan proteins (AGPs are a highly diverse class of cell surface proteoglycans that are commonly found in most plant species. AGPs play important roles in many cellular processes during plant development, such as reproduction, cell proliferation, pattern formation and growth, and in plant-microbe interaction. However, little is known about the molecular mechanisms of their function. Numerous studies using monoclonal antibodies that recognize different AGP glycan epitopes have shown the appearance of a slightly altered AGP glycan in a specific stage of development in plant cells. Therefore, it is anticipated that the biosynthesis and degradation of AGP glycan is tightly regulated during development. Until recently, however, little was known about the enzymes involved in the metabolism of AGP glycans. In this review, we summarize recent discoveries of carbohydrate active enzymes (CAZy; http://www.cazy.org/ involved in the biosynthesis and degradation of AGP glycans, and we discuss the biological role of these enzymes in plant development.

  15. Using Carbohydrate Interaction Assays to Reveal Novel Binding Sites in Carbohydrate Active Enzymes

    DEFF Research Database (Denmark)

    Cockburn, Darrell; Wilkens, Casper; Dilokpimol, Adiphol;

    2016-01-01

    Carbohydrate active enzymes often contain auxiliary binding sites located either on independent domains termed carbohydrate binding modules (CBMs) or as so-called surface binding sites (SBSs) on the catalytic module at a certain distance from the active site. The SBSs are usually critical...... for the activity of their cognate enzyme, though they are not readily detected in the sequence of a protein, but normally require a crystal structure of a complex for their identification. A variety of methods, including affinity electrophoresis (AE), insoluble polysaccharide pulldown (IPP) and surface plasmon...... resonance (SPR) have been used to study auxiliary binding sites. These techniques are complementary as AE allows monitoring of binding to soluble polysaccharides, IPP to insoluble polysaccharides and SPR to oligosaccharides. Here we show that these methods are useful not only for analyzing known binding...

  16. Sensitive LC MS quantitative analysis of carbohydrates by Cs+ attachment.

    Science.gov (United States)

    Rogatsky, Eduard; Jayatillake, Harsha; Goswami, Gayotri; Tomuta, Vlad; Stein, Daniel

    2005-11-01

    The development of a sensitive assay for the quantitative analysis of carbohydrates from human plasma using LC/MS/MS is described in this paper. After sample preparation, carbohydrates were cationized by Cs(+) after their separation by normal phase liquid chromatography on an amino based column. Cesium is capable of forming a quasi-molecular ion [M + Cs](+) with neutral carbohydrate molecules in the positive ion mode of electrospray ionization mass spectrometry. The mass spectrometer was operated in multiple reaction monitoring mode, and transitions [M + 133] --> 133 were monitored (M, carbohydrate molecular weight). The new method is robust, highly sensitive, rapid, and does not require postcolumn addition or derivatization. It is useful in clinical research for measurement of carbohydrate molecules by isotope dilution assay. PMID:16182559

  17. Mining anaerobic digester consortia metagenomes for secreted carbohydrate active enzymes

    DEFF Research Database (Denmark)

    Wilkens, Casper; Busk, Peter Kamp; Pilgaard, Bo;

    . To gain insight into both the degradation of the carbohydrates and the various roles of the microbes in the ADs we have mined metagenomes from both types of ADs for glycoside hydrolases, carbohydrate esterases, polysaccharide lyases, auxiliary activities, and carbohydrate binding modules. The mining...... thermophilic and mesophilic ADs a wide variety of carbohydrate active enzyme functions were discovered in the metagenomic sequencing of the microbial consortia. The most dominating type of glycoside hydrolases were β-glucosidases (up to 27%), α-amylases (up to 10%), α-glucosidases (up to 8%), α......-galactosidases (up to 9%) and β-galactosidases (up to 7%). For carbohydrate esterases the by far most dominating type was acetylxylan esterases (up to 59%) followed by feruloyl esterases (up to 16%). Less than 15 polysaccharide lyases were identified in the different metagenomes and not surprisingly...

  18. Relationship of carbohydrate molecular spectroscopic features in combined feeds to carbohydrate utilization and availability in ruminants

    Science.gov (United States)

    Zhang, Xuewei; Yu, Peiqiang

    To date, there is no study on the relationship between carbohydrate (CHO) molecular structures and nutrient availability of combined feeds in ruminants. The objective of this study was to use molecular spectroscopy to reveal the relationship between CHO molecular spectral profiles (in terms of functional groups (biomolecular, biopolymer) spectral peak area and height intensity) and CHO chemical profiles, CHO subfractions, energy values, and CHO rumen degradation kinetics of combined feeds of hulless barley with pure wheat dried distillers grains with solubles (DDGS) at five different combination ratios (hulless barley to pure wheat DDGS: 100:0, 75:25, 50:50, 25:75, 0:100). The molecular spectroscopic parameters assessed included: lignin biopolymer molecular spectra profile (peak area and height, region and baseline: ca. 1539-1504 cm-1); structural carbohydrate (STCHO, peaks area region and baseline: ca. 1485-1186 cm-1) mainly associated with hemi- and cellulosic compounds; cellulosic materials peak area (centered at ca. 1240 cm-1 with region and baseline: ca. 1272-1186 cm-1); total carbohydrate (CHO, peaks area region and baseline: ca. 1186-946 cm-1). The results showed that the functional groups (biomolecular, biopolymer) in the combined feeds are sensitive to the changes of carbohydrate chemical and nutrient profiles. The changes of the CHO molecular spectroscopic features in the combined feeds were highly correlated with CHO chemical profiles, CHO subfractions, in situ CHO rumen degradation kinetics and fermentable organic matter supply. Further study is needed to investigate possibility of using CHO molecular spectral features as a predictor to estimate nutrient availability in combined feeds for animals and quantify their relationship.

  19. Renewable Hydrogen Carrier — Carbohydrate: Constructing the Carbon-Neutral Carbohydrate Economy

    OpenAIRE

    Y.-H. Percival Zhang; Mielenz, Jonathan R.

    2011-01-01

    The hydrogen economy presents an appealing energy future but its implementation must solve numerous problems ranging from low-cost sustainable production, high-density storage, costly infrastructure, to eliminating safety concern. The use of renewable carbohydrate as a high-density hydrogen carrier and energy source for hydrogen production is possible due to emerging cell-free synthetic biology technology—cell-free synthetic pathway biotransformation (SyPaB). Assembly of numerous enzymes and ...

  20. Renewable Hydrogen Carrier — Carbohydrate: Constructing the Carbon-Neutral Carbohydrate Economy

    OpenAIRE

    Y.-H. Percival Zhang; Mielenz, Jonathan R.

    2011-01-01

    The hydrogen economy presents an appealing energy future but its implementation must solve numerous problems ranging from low-cost sustainable production, high-density storage, costly infrastructure, to eliminating safety concern. The use of renewable carbohydrate as a high-density hydrogen carrier and energy source for hydrogen production is possible due to emerging cell-free synthetic biology technology–cell-free synthetic pathway biotransformation (SyPaB). Assembly of numerous enzymes and ...

  1. Blood Triglycerides Levels and Dietary Carbohydrate Indices in Healthy Koreans

    Science.gov (United States)

    Kang, Ji Yeon

    2016-01-01

    Objectives: Previous studies have obtained conflicting findings regarding possible associations between indices measuring carbohydrate intake and dyslipidemia, which is an established risk factor of coronary heart disease. In the present study, we examined cross-sectional associations between carbohydrate indices, including the dietary glycemic index (GI), glycemic load (GL), total amount of carbohydrates, and the percentage of energy from carbohydrates, and a range of blood lipid parameters. Methods: This study included 1530 participants (554 men and 976 women) from 246 families within the Healthy Twin Study. We analyzed the associations using a generalized linear mixed model to control for familial relationships. Results: Levels of the Apo B were inversely associated with dietary GI, GL, and the amount of carbohydrate intake for men, but these relationships were not significant when fat-adjusted values of the carbohydrate indices were used. Triglyceride levels were positively associated with dietary GI and GL in women, and this pattern was more notable in overweight participants (body mass index [BMI] ≥25 kg/m2). However, total, low-density lipoprotein and high-density lipoprotein cholesterol levels were not significantly related with carbohydrate intake overall. Conclusions: Of the blood lipid parameters we investigated, only triglyceride levels were positively related with dietary carbohydrate indices among women participants in the Healthy Twin Study, with an interactive role observed for BMI. However, these associations were not observed in men, suggesting that the association between blood lipid levels and carbohydrate intake depends on the type of lipid, specific carbohydrate indices, gender, and BMI. PMID:27255074

  2. The case for low carbohydrate diets in diabetes management

    Directory of Open Access Journals (Sweden)

    McFarlane Samy I

    2005-07-01

    Full Text Available Abstract A low fat, high carbohydrate diet in combination with regular exercise is the traditional recommendation for treating diabetes. Compliance with these lifestyle modifications is less than satisfactory, however, and a high carbohydrate diet raises postprandial plasma glucose and insulin secretion, thereby increasing risk of CVD, hypertension, dyslipidemia, obesity and diabetes. Moreover, the current epidemic of diabetes and obesity has been, over the past three decades, accompanied by a significant decrease in fat consumption and an increase in carbohydrate consumption. This apparent failure of the traditional diet, from a public health point of view, indicates that alternative dietary approaches are needed. Because carbohydrate is the major secretagogue of insulin, some form of carbohydrate restriction is a prima facie candidate for dietary control of diabetes. Evidence from various randomized controlled trials in recent years has convinced us that such diets are safe and effective, at least in short-term. These data show low carbohydrate diets to be comparable or better than traditional low fat high carbohydrate diets for weight reduction, improvement in the dyslipidemia of diabetes and metabolic syndrome as well as control of blood pressure, postprandial glycemia and insulin secretion. Furthermore, the ability of low carbohydrate diets to reduce triglycerides and to increase HDL is of particular importance. Resistance to such strategies has been due, in part, to equating it with the popular Atkins diet. However, there are many variations and room for individual physician planning. Some form of low carbohydrate diet, in combination with exercise, is a viable option for patients with diabetes. However, the extreme reduction of carbohydrate of popular diets (

  3. Comparative analysis of carbohydrate active enzymes in Clostridium termitidis CT1112 reveals complex carbohydrate degradation ability.

    Directory of Open Access Journals (Sweden)

    Riffat I Munir

    Full Text Available Clostridium termitidis strain CT1112 is an anaerobic, gram positive, mesophilic, cellulolytic bacillus isolated from the gut of the wood-feeding termite, Nasutitermes lujae. It produces biofuels such as hydrogen and ethanol from cellulose, cellobiose, xylan, xylose, glucose, and other sugars, and therefore could be used for biofuel production from biomass through consolidated bioprocessing. The first step in the production of biofuel from biomass by microorganisms is the hydrolysis of complex carbohydrates present in biomass. This is achieved through the presence of a repertoire of secreted or complexed carbohydrate active enzymes (CAZymes, sometimes organized in an extracellular organelle called cellulosome. To assess the ability and understand the mechanism of polysaccharide hydrolysis in C. termitidis, the recently sequenced strain CT1112 of C. termitidis was analyzed for both CAZymes and cellulosomal components, and compared to other cellulolytic bacteria. A total of 355 CAZyme sequences were identified in C. termitidis, significantly higher than other Clostridial species. Of these, high numbers of glycoside hydrolases (199 and carbohydrate binding modules (95 were identified. The presence of a variety of CAZymes involved with polysaccharide utilization/degradation ability suggests hydrolysis potential for a wide range of polysaccharides. In addition, dockerin-bearing enzymes, cohesion domains and a cellulosomal gene cluster were identified, indicating the presence of potential cellulosome assembly.

  4. Comparative analysis of carbohydrate active enzymes in Clostridium termitidis CT1112 reveals complex carbohydrate degradation ability.

    Science.gov (United States)

    Munir, Riffat I; Schellenberg, John; Henrissat, Bernard; Verbeke, Tobin J; Sparling, Richard; Levin, David B

    2014-01-01

    Clostridium termitidis strain CT1112 is an anaerobic, gram positive, mesophilic, cellulolytic bacillus isolated from the gut of the wood-feeding termite, Nasutitermes lujae. It produces biofuels such as hydrogen and ethanol from cellulose, cellobiose, xylan, xylose, glucose, and other sugars, and therefore could be used for biofuel production from biomass through consolidated bioprocessing. The first step in the production of biofuel from biomass by microorganisms is the hydrolysis of complex carbohydrates present in biomass. This is achieved through the presence of a repertoire of secreted or complexed carbohydrate active enzymes (CAZymes), sometimes organized in an extracellular organelle called cellulosome. To assess the ability and understand the mechanism of polysaccharide hydrolysis in C. termitidis, the recently sequenced strain CT1112 of C. termitidis was analyzed for both CAZymes and cellulosomal components, and compared to other cellulolytic bacteria. A total of 355 CAZyme sequences were identified in C. termitidis, significantly higher than other Clostridial species. Of these, high numbers of glycoside hydrolases (199) and carbohydrate binding modules (95) were identified. The presence of a variety of CAZymes involved with polysaccharide utilization/degradation ability suggests hydrolysis potential for a wide range of polysaccharides. In addition, dockerin-bearing enzymes, cohesion domains and a cellulosomal gene cluster were identified, indicating the presence of potential cellulosome assembly.

  5. Carbohydrate-enriched cyanobacterial biomass as feedstock for bio-methane production through anaerobic digestion

    DEFF Research Database (Denmark)

    Markou, Giorgos; Angelidaki, Irini; Georgakakis, Dimitris

    2013-01-01

    The anaerobic digestion performance using carbohydrate-enriched biomass of Arthrospira platensis was studied. The carbohydrate enrichment was achieved after the cultivation of A. platensis under phosphorus limitation conditions. Three biomass compositions (60%, 40% and 20% carbohydrates content) ...

  6. Dietary non-digestible carbohydrates and the resistance to intestinal infections

    NARCIS (Netherlands)

    Bruggencate, ten S.J.M.

    2004-01-01

    Keywords: Non-digestible carbohydrates, prebiotics, inulin, FOS, calcium, microflora, short-chain fatty acids, mucin, intestinal permeability, salmonella, infection, rat, humanDietary non-digestible carbohydrates and the resistance to intestinal infectionsNon-digestible carbohydrates (NDC) stimulate

  7. Carbohydrate Content in the GDM Diet: Two Views: View 1: Nutrition Therapy in Gestational Diabetes: The Case for Complex Carbohydrates.

    Science.gov (United States)

    Hernandez, Teri L

    2016-05-01

    IN BRIEF Restriction of dietary carbohydrate has been the cornerstone for treatment of gestational diabetes mellitus (GDM). However, there is evidence that a balanced liberalization of complex carbohydrate as part of an overall eating plan in GDM meets treatment goals and may mitigate maternal adipose tissue insulin resistance, both of which may promote optimal metabolic outcomes for mother and offspring.

  8. [Performance enhancement by carbohydrate intake during sport: effects of carbohydrates during and after high-intensity exercise].

    Science.gov (United States)

    Beelen, Milou; Cermak, Naomi M; van Loon, Luc J C

    2015-01-01

    Endogenous carbohydrate availability does not provide sufficient energy for prolonged moderate to high-intensity exercise. Carbohydrate ingestion during high-intensity exercise can therefore enhance performance.- For exercise lasting 1 to 2.5 hours, athletes are advised to ingest 30-60 g of carbohydrates per hour.- Well-trained endurance athletes competing for longer than 2.5 hours at high intensity can metabolise up to 90 g of carbohydrates per hour, provided that a mixture of glucose and fructose is ingested.- Athletes participating in intermittent or team sports are advised to follow the same strategies but the timing of carbohydrate intake depends on the type of sport.- If top performance is required again within 24 hours after strenuous exercise, the advice is to supplement endogenous carbohydrate supplies quickly within the first few hours post-exercise by ingesting large amounts of carbohydrate (1.2 g/kg/h) or a lower amount of carbohydrate (0.8 g/kg/h) with a small amount of protein (0.2-0.4 g/kg/h).

  9. Vaccination with an adenoviral vector encoding the tumor antigen directly linked to invariant chain induces potent CD4(+) T-cell-independent CD8(+) T-cell-mediated tumor control

    DEFF Research Database (Denmark)

    Sorensen, Maria R; Holst, Peter J; Pircher, Hanspeter;

    2009-01-01

    of the vaccine antigen to invariant chain (Ii). To evaluate this strategy we used a mouse model, in which an immunodominant epitope (GP33) of the LCMV glycoprotein (GP) represents the tumor-associated neoantigen. Prophylactic vaccination of C57BL/6 mice with a replication-deficient human adenovirus 5 vector...... vaccination with adenovirus expressing GP alone (Ad-GP), or GP and Ii unlinked (Ad-GP+Ii). Ad-Ii-GP- induced tumor control depended on an improved generation of the tumor-associated neoantigen-specific CD8(+) T-cell response and was independent of CD4(+) T cells. IFN-gamma was shown to be a key player during...

  10. Cyclic enterobacterial common antigen: Potential contaminant of bacterially expressed protein preparations

    International Nuclear Information System (INIS)

    We have previously reported the identification of the cyclic enterobacterial common antigen (ECACYC) polysaccharide in E. coli strains commonly used for heterologous protein expression (PJA Erbel et al., J. Bacteriol.185 (2003): 1995). Following this initial report, interactions among several NMR groups established that characteristic N-acetyl signals of ECACYC have been observed in 15N-1H HSQC spectra of samples of various bacterially-expressed proteins suggesting that this water-soluble carbohydrate is a common contaminant. We provide NMR spectroscopic tools to recognize ECACYC in protein samples, as well as several methods to remove this contaminant. Early recognition of ECA-based NMR signals will prevent time-consuming analyses of this copurifying carbohydrate

  11. Definition of a physiologic aging autoantigen by using synthetic peptides of membrane protein band 3: localization of the active antigenic sites.

    Science.gov (United States)

    Kay, M M; Marchalonis, J J; Hughes, J; Watanabe, K; Schluter, S F

    1990-08-01

    Senescent cell antigen (SCA), an aging antigen, is a protein that appears on old cells and marks them for removal by the immune system in mammals. It is derived from band 3, a ubiquitous membrane transport protein found in diverse cell types and tissues. We have used synthetic peptides to identify aging antigenic sites on band 3, using a competitive inhibition assay and immunoblotting with IgG directed against the aging antigen on old cells. Results indicate that: (i) the active antigenic sites of the aging antigen reside on membrane protein band 3 residues that are extracellular regions implicated in anion transport (residues 538-554 and 788-827); (ii) a putative ankyrin-binding-region peptide is not involved in SCA activity; and (iii) carbohydrate moieties are not required for the antigenicity or recognition of SCA because synthetic peptides alone abolish binding of senescent cell IgG to erythrocytes. One of the putative transport sites that contributes to the aging antigen is located toward the carboxyl terminus. A model of band 3 is presented. Localization of the active antigenic site on the band 3 molecule facilitates definition of the molecular changes occurring during aging that initiate molecular as well as cellular degeneration. PMID:1696010

  12. [Farmer's lung antigens in Germany].

    Science.gov (United States)

    Sennekamp, J; Joest, M; Sander, I; Engelhart, S; Raulf-Heimsoth, M

    2012-05-01

    Recent studies suggest that besides the long-known farmer's lung antigen sources Saccharopolyspora rectivirgula (Micropolyspora faeni), Thermoactinomyces vulgaris, and Aspergillus fumigatus, additionally the mold Absidia (Lichtheimia) corymbifera as well as the bacteria Erwinia herbicola (Pantoea agglomerans) and Streptomyces albus may cause farmer's lung in Germany. In this study the sera of 64 farmers with a suspicion of farmer's lung were examined for the following further antigens: Wallemia sebi, Cladosporium herbarum, Aspergillus versicolor, and Eurotium amstelodami. Our results indicate that these molds are not frequent causes of farmer's lung in Germany. PMID:22477566

  13. Identifying Carbohydrate Ligands of a Norovirus P Particle using a Catch and Release Electrospray Ionization Mass Spectrometry Assay

    Science.gov (United States)

    Han, Ling; Kitova, Elena N.; Tan, Ming; Jiang, Xi; Klassen, John S.

    2014-01-01

    Noroviruses (NoVs), the major cause of epidemic acute gastroenteritis, recognize human histo-blood group antigens (HBGAs), which are present as free oligosaccharides in bodily fluid or glycolipids and glycoproteins on the surfaces of cells. The subviral P particle formed by the protruding (P) domain of the NoV capsid protein serves as a useful model for the study NoV-HBGA interactions. Here, we demonstrate the application of a catch-and-release electrospray ionization mass spectrometry (CaR-ESI-MS) assay for screening carbohydrate libraries against the P particle to rapidly identify NoV ligands and potential inhibitors. Carbohydrate libraries of 50 and 146 compounds, which included 18 and 24 analogs of HBGA receptors, respectively, were screened against the P particle of VA387, a member of the predominant GII.4 NoVs. Deprotonated ions corresponding to the P particle bound to carbohydrates were isolated and subjected to collision-induced dissociation to release the ligands in their deprotonated forms. The released ligands were identified by ion mobility separation followed by mass analysis. All 13 and 16 HBGA ligands with intrinsic affinities >500 M-1 were identified in the 50 and the 146 compound libraries, respectively. Furthermore, screening revealed interactions with a series of oligosaccharides with structures found in the cell wall of mycobacteria and human milk. The affinities of these newly discovered ligands are comparable to those of the HBGA receptors, as estimated from the relative abundance of released ligand ions.

  14. Adoptive immunotherapy for acute leukemia:New insights in chimeric antigen receptors

    Institute of Scientific and Technical Information of China (English)

    Ma?l; Heiblig; Mohamed; Elhamri; Mauricette; Michallet; Xavier; Thomas

    2015-01-01

    Relapses remain a major concern in acute leukemia. It is well known that leukemia stem cells(LSCs) hide in hematopoietic niches and escape to the immune system surveillance through the outgrowth of poorly immunogenic tumor-cell variants and the suppression of the active immune response. Despitethe introduction of new reagents and new therapeutic approaches, no treatment strategies have been able to definitively eradicate LSCs. However, recent adoptive immunotherapy in cancer is expected to revolutionize our way to fight against this disease, by redirecting the immune system in order to eliminate relapse issues. Initially described at the onset of the 90’s, chimeric antigen receptors(CARs) are recombinant receptors transferred in various T cell subsets, providing specific antigens binding in a non-major histocompatibility complex restricted manner, and effective on a large variety of human leukocyte antigen-divers cell populations. Once transferred, engineered T cells act like an expanding "living drug" specifically targeting the tumor-associated antigen, and ensure long-term antitumor memory. Over the last decades, substantial improvements have been made in CARs design. CAR T cells have finally reached the clinical practice and first clinical trials have shown promising results. In acute lymphoblastic leukemia, high rate of complete and prolonged clinical responses have been observed after anti-CD19 CAR T cell therapy, with specific but manageable adverse events. In this review, our goal was to describe CAR structures and functions, and to summarize recent data regarding pre-clinical studies and clinical trials in acute leukemia.

  15. Assessing Bacterial Interactions Using Carbohydrate-Based Microarrays

    Directory of Open Access Journals (Sweden)

    Andrea Flannery

    2015-12-01

    Full Text Available Carbohydrates play a crucial role in host-microorganism interactions and many host glycoconjugates are receptors or co-receptors for microbial binding. Host glycosylation varies with species and location in the body, and this contributes to species specificity and tropism of commensal and pathogenic bacteria. Additionally, bacterial glycosylation is often the first bacterial molecular species encountered and responded to by the host system. Accordingly, characterising and identifying the exact structures involved in these critical interactions is an important priority in deciphering microbial pathogenesis. Carbohydrate-based microarray platforms have been an underused tool for screening bacterial interactions with specific carbohydrate structures, but they are growing in popularity in recent years. In this review, we discuss carbohydrate-based microarrays that have been profiled with whole bacteria, recombinantly expressed adhesins or serum antibodies. Three main types of carbohydrate-based microarray platform are considered; (i conventional carbohydrate or glycan microarrays; (ii whole mucin microarrays; and (iii microarrays constructed from bacterial polysaccharides or their components. Determining the nature of the interactions between bacteria and host can help clarify the molecular mechanisms of carbohydrate-mediated interactions in microbial pathogenesis, infectious disease and host immune response and may lead to new strategies to boost therapeutic treatments.

  16. Sugar for my honey: carbohydrate partitioning in ectomycorrhizal symbiosis.

    Science.gov (United States)

    Nehls, Uwe; Grunze, Nina; Willmann, Martin; Reich, Marlis; Küster, Helge

    2007-01-01

    Simple, readily utilizable carbohydrates, necessary for growth and maintenance of large numbers of microbes are rare in forest soils. Among other types of mutualistic interactions, the formation of ectomycorrhizas, a symbiosis between tree roots and certain soil fungi, is a way to overcome nutrient and carbohydrate limitations typical for many forest ecosystems. Ectomycorrhiza formation is typical for trees in boreal and temperate forests of the northern hemisphere and alpine regions world-wide. The main function of this symbiosis is the exchange of fungus-derived nutrients for plant-derived carbohydrates, enabling the colonization of mineral nutrient-poor environments. In ectomycorrhizal symbiosis up to 1/3 of plant photoassimilates could be transferred toward the fungal partner. The creation of such a strong sink is directly related to the efficiency of fungal hexose uptake at the plant/fungus interface, a modulated fungal carbohydrate metabolism in the ectomycorrhiza, and the export of carbohydrates towards soil growing hyphae. However, not only the fungus but also the plant partner increase its expression of hexose importer genes at the plant/fungus interface. This increase in hexose uptake capacity of plant roots in combination with an increase in photosynthesis may explain how the plant deals with the growing fungal carbohydrate demand in symbiosis and how it can restrict this loss of carbohydrates under certain conditions to avoid fungal parasitism. PMID:17078984

  17. Linking Bacillus cereus Genotypes and Carbohydrate Utilization Capacity.

    Science.gov (United States)

    Warda, Alicja K; Siezen, Roland J; Boekhorst, Jos; Wells-Bennik, Marjon H J; de Jong, Anne; Kuipers, Oscar P; Nierop Groot, Masja N; Abee, Tjakko

    2016-01-01

    We characterised carbohydrate utilisation of 20 newly sequenced Bacillus cereus strains isolated from food products and food processing environments and two laboratory strains, B. cereus ATCC 10987 and B. cereus ATCC 14579. Subsequently, genome sequences of these strains were analysed together with 11 additional B. cereus reference genomes to provide an overview of the different types of carbohydrate transporters and utilization systems found in B. cereus strains. The combined application of API tests, defined growth media experiments and comparative genomics enabled us to link the carbohydrate utilisation capacity of 22 B. cereus strains with their genome content and in some cases to the panC phylogenetic grouping. A core set of carbohydrates including glucose, fructose, maltose, trehalose, N-acetyl-glucosamine, and ribose could be used by all strains, whereas utilisation of other carbohydrates like xylose, galactose, and lactose, and typical host-derived carbohydrates such as fucose, mannose, N-acetyl-galactosamine and inositol is limited to a subset of strains. Finally, the roles of selected carbohydrate transporters and utilisation systems in specific niches such as soil, foods and the human host are discussed. PMID:27272929

  18. Linking Bacillus cereus Genotypes and Carbohydrate Utilization Capacity

    Science.gov (United States)

    Warda, Alicja K.; Siezen, Roland J.; Boekhorst, Jos; Wells-Bennik, Marjon H. J.; de Jong, Anne; Kuipers, Oscar P.; Nierop Groot, Masja N.; Abee, Tjakko

    2016-01-01

    We characterised carbohydrate utilisation of 20 newly sequenced Bacillus cereus strains isolated from food products and food processing environments and two laboratory strains, B. cereus ATCC 10987 and B. cereus ATCC 14579. Subsequently, genome sequences of these strains were analysed together with 11 additional B. cereus reference genomes to provide an overview of the different types of carbohydrate transporters and utilization systems found in B. cereus strains. The combined application of API tests, defined growth media experiments and comparative genomics enabled us to link the carbohydrate utilisation capacity of 22 B. cereus strains with their genome content and in some cases to the panC phylogenetic grouping. A core set of carbohydrates including glucose, fructose, maltose, trehalose, N-acetyl-glucosamine, and ribose could be used by all strains, whereas utilisation of other carbohydrates like xylose, galactose, and lactose, and typical host-derived carbohydrates such as fucose, mannose, N-acetyl-galactosamine and inositol is limited to a subset of strains. Finally, the roles of selected carbohydrate transporters and utilisation systems in specific niches such as soil, foods and the human host are discussed. PMID:27272929

  19. Linking Bacillus cereus Genotypes and Carbohydrate Utilization Capacity.

    Directory of Open Access Journals (Sweden)

    Alicja K Warda

    Full Text Available We characterised carbohydrate utilisation of 20 newly sequenced Bacillus cereus strains isolated from food products and food processing environments and two laboratory strains, B. cereus ATCC 10987 and B. cereus ATCC 14579. Subsequently, genome sequences of these strains were analysed together with 11 additional B. cereus reference genomes to provide an overview of the different types of carbohydrate transporters and utilization systems found in B. cereus strains. The combined application of API tests, defined growth media experiments and comparative genomics enabled us to link the carbohydrate utilisation capacity of 22 B. cereus strains with their genome content and in some cases to the panC phylogenetic grouping. A core set of carbohydrates including glucose, fructose, maltose, trehalose, N-acetyl-glucosamine, and ribose could be used by all strains, whereas utilisation of other carbohydrates like xylose, galactose, and lactose, and typical host-derived carbohydrates such as fucose, mannose, N-acetyl-galactosamine and inositol is limited to a subset of strains. Finally, the roles of selected carbohydrate transporters and utilisation systems in specific niches such as soil, foods and the human host are discussed.

  20. Characterization of carbohydrates in rainwater from the southeastern North Carolina.

    Science.gov (United States)

    Mullaugh, Katherine M; Byrd, Jade N; Avery, G Brooks; Mead, Ralph N; Willey, Joan D; Kieber, Robert J

    2014-07-01

    Carbohydrates have been widely reported in atmospheric aerosols, but have not previously been quantified in rainwater. We have identified and quantified a series of 11 specific compounds including monosaccharides (glucose, fructose, arabinose, galactose and pinitol), disaccharides (sucrose and trehalose), sugar alcohols (arabitol, dulcitol and mannitol) and the anhydrosaccharide levoglucosan. Rainwater analyzed in this study includes 52 distinct precipitation events in Wilmington, NC between June 2011 and October 2012. Our analysis indicates carbohydrates typically contribute carbohydrates reached as high as 5.8 μM, with glucose and sucrose typically being the predominant species. The distribution of carbohydrates exhibited a distinct seasonal pattern, with higher concentrations of most carbohydrates, especially sucrose, in spring and summer, driven primarily by increased biogenic inputs during the growing season. Concentrations of carbohydrates were an order of magnitude higher in storms of terrestrial origin compared to marine events, further supporting a terrestrial biogenic origin of most species. Sequential sampling of Hurricane Irene showed significant quantities of carbohydrates present at the end of the storm when air mass back trajectories traversed over land. The highest level of levoglucosan, a compound associated with biomass burning, was detected in rain with an air mass back trajectory that traveled over a region affected by wildfires. When compared to aerosol concentrations reported by others, the sugar concentrations in rain demonstrate wet deposition is an important removal mechanism of this water-soluble and bioavailable fraction of atmospheric particulate organic matter.

  1. Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations.

    Directory of Open Access Journals (Sweden)

    Laura A Laviolette

    Full Text Available The Birt-Hogg-Dube disease occurs as a result of germline mutations in the human Folliculin gene (FLCN, and is characterized by clinical features including fibrofolliculomas, lung cysts and multifocal renal neoplasia. Clinical and genetic evidence suggest that FLCN acts as a tumor suppressor gene. The human cell line UOK257, derived from the renal cell carcinoma of a patient with a germline mutation in the FLCN gene, harbors a truncated version of the FLCN protein. Reconstitution of the wild type FLCN protein into UOK257 cells delays cell cycle progression, due to a slower progression through the late S and G2/M-phases. Similarly, Flcn (-/- mouse embryonic fibroblasts progress more rapidly through the cell cycle than wild type controls (Flcn (flox/flox. The reintroduction of tumor-associated FLCN mutants (FLCN ΔF157, FLCN 1-469 or FLCN K508R fails to delay cell cycle progression in UOK257 cells. Additionally, FLCN phosphorylation (on Serines 62 and 73 fluctuates throughout the cell cycle and peaks during the G2/M phase in cells treated with nocodazole. In keeping with this observation, the reintroduction of a FLCN phosphomimetic mutant into the UOK257 cell line results in faster progression through the cell cycle compared to those expressing the wild type FLCN protein. These findings suggest that the tumor suppression function of FLCN may be linked to its impact on the cell cycle and that FLCN phosphorylation is important for this activity. Additionally, these observations describe a novel in vitro assay for testing the functional significance of FLCN mutations and/or genetic polymorphisms.

  2. Expression of Cathepsin L in tumor cells and tumor-associated macrophages in patients with Ewing sarcoma family of tumors: A pilot study

    Directory of Open Access Journals (Sweden)

    Bivas Biswas

    2015-01-01

    Full Text Available Background: Cysteine protease Cathepsin L is involved in bone remodeling and expressed in activated macrophages. It is highly expressed in metastatic tumor tissue, especially with bone metastases. Aims: We evaluated immunohistochemical expression of Cathepsin L in tumor cells and tumor-associated macrophages (TAMs in chemo-naive Ewing sarcoma. Settings and Design: Retrospective evaluation of archived specimens of Ewing sarcoma. Materials and Methods: Immunohistochemical staining was performed on archived blocks of chemo-naive patients with Ewing sarcoma treated with uniform chemotherapy at our institute between January 2009 and November 2011. Statistical Analysis: Immunohistochemical expression was co-related with baseline demographics and survival. Results: During the study period, we had evaluable baseline samples from 62 patients with median age 15 years (range: 2-40; 26 (42% had metastases. Cathepsin L expression in tumor cells was observed in 8/62 (13% specimens. None of the baseline clinical characteristics correlated with Cathepsin L expression. Cathepsin L positivity was associated with poor response to neoadjuvant chemotherapy (NACT (P = 0.05, but did not influence either event-free-survival (EFS or overall survival. Cathepsin L was expressed in TAMs in all specimens. Grade 3 TAMs (>10 TAMs/high power field was associated with better response to NACT (P = 0.05. On univariate analysis Grade 3 TAMs predicted superior EFS (median EFS 28.5 months in those with Grade 3 TAMs versus 14.8 months in those with grade ½ TAMs [P = 0.04]. Conclusions: Cathepsin L expression by immunohistochemistry was low in our patient cohort, and it did not affect the outcome. In addition, Grade 3 TAMs with Cathepsin L expression was associated with improved EFS.

  3. Shiga toxin receptor Gb3Cer/CD77: tumor-association and promising therapeutic target in pancreas and colon cancer.

    Directory of Open Access Journals (Sweden)

    Ute Distler

    Full Text Available BACKGROUND: Despite progress in adjuvant chemotherapy in the recent decades, pancreatic and colon cancers remain common causes of death worldwide. Bacterial toxins, which specifically bind to cell surface-exposed glycosphingolipids, are a potential novel therapy. We determined the expression of globotriaosylceramide (Gb3Cer/CD77, the Shiga toxin receptor, in human pancreatic and colon adenocarcinomas. METHODOLOGY/PRINCIPAL FINDINGS: Tissue lipid extracts of matched pairs of cancerous and adjacent normal tissue from 21 pancreatic and 16 colon cancer patients were investigated with thin-layer chromatography overlay assay combined with a novel mass spectrometry approach. Gb3Cer/CD77 was localized by immunofluorescence microscopy of cryosections from malignant and corresponding healthy tissue samples. 62% of pancreatic and 81% of colon adenocarcinomas showed increased Gb3Cer/CD77 expression, whereas 38% and 19% of malignant pancreas and colon tissue, respectively, did not, indicating an association of this marker with neoplastic transformation. Also, Gb3Cer/CD77 was associated with poor differentiation (G>2 in pancreatic cancer (P = 0.039. Mass spectrometric analysis evidenced enhanced expression of Gb3Cer/CD77 with long (C24 and short chain fatty acids (C16 in malignant tissues and pointed to the presence of hydroxylated fatty acid lipoforms, which are proposed to be important for receptor targeting. They could be detected in 86% of pancreatic and about 19% of colon adenocarcinomas. Immunohistology of tissue cryosections indicated tumor-association of these receptors. CONCLUSIONS/SIGNIFICANCE: Enhanced expression of Gb3Cer/CD77 in most pancreatic and colon adenocarcinomas prompts consideration of Shiga toxin, its B-subunit or B-subunit-derivatives as novel therapeutic strategies for the treatment of these challenging malignancies.

  4. Evaluation of myeloid cells (tumor-associated tissue eosinophils and mast cells) infiltration in different grades of oral squamous cell carcinoma

    Science.gov (United States)

    Debta, Priyanka; Debta, Fakir Mohan; Chaudhary, Minal; Bussari, Smita

    2016-01-01

    Background: The multifunctional involvement and infiltration of myeloid cells (tumor-associated tissue eosinophils [TATE] and mast cells) can provide a unique opportunity to define relevant effectors functions that may represent novel, therapeutic options for modulation of tumor onset/growth. Aim: Our study aimed to evaluate infiltration of myeloid cells (TATE and Mast cells) infiltration in different grades (WHO grading) of oral squamous cell carcinoma (OSCC). Materials and Methods: Total 30 cases of OSCC were selected for this study. Hematoxylin and eosin stain and toluidine blue special stain, to evaluate TATE and the mast cells infiltration, were used. Three-year follow-up of OSCC cases was done. Result: Among 30 cases, 63.33% cases of OSCC showed TATE-positive and 36.66% cases showed TATE-negative. Regarding mast cells infiltration, 66.66% OSCC cases showed mast cells positive and 33.33% cases did not show significant mast cells infiltration. We found significant association of TATE and mast cells infiltration in OSCC cases. These myeloid cells infiltration significantly associated with age of patients but did not show any significant association with gender, site, and habit of cases. When we compared these cells infiltration with clinical stages and different histological grades of tumor, we found their infiltration is decreasing, from Stages 1 to Stage 3 of tumor and from well to poorly differentiated carcinoma. We have also found the less infiltration of these myeloid in recurrence cases of OSCC. Conclusion: As the infiltration of TATE and mast cells are correlated, along with evaluation of TATE, we should also evaluate the presence of mast cells infiltration in OSCC. The assessment of myeloid cells could become, in the future, useful for therapeutic approaches in this subset of the patient. PMID:27688609

  5. Vasohibin-1 Expression Is Regulated by Transforming Growth Factor-β/Bone Morphogenic Protein Signaling Pathway Between Tumor-Associated Macrophages and Pancreatic Cancer Cells

    Science.gov (United States)

    Seppänen, Hanna; Kauttu, Tuuli; Vainionpää, Sanna; Ye, Yingjiang; Mustonen, Harri

    2013-01-01

    Vasohibin-1 has been detected in endothelial cells as an intrinsic angiogenesis inhibitor. Both tumor-associated macrophages (TAMs) and transforming growth factor-β (TGF-β)/bone morphogenic protein (BMP) signaling have been reported to promote angiogenesis in cancer. However, whether vasohibin-1 expression is regulated by TGF-β/BMP signaling between TAMs and cancer cells remains unclear. The expression of TGF-β1, TGF-β2, BMP-4, and BMP-7 in TAMs and the expression of vasohibin-1, vascular endothelial growth factor-A (VEGF-A), and VEGF-C in two pancreatic cancer cell lines (a nonmetastatic cell line Panc-1 and a distant metastatic cell line HPAF-II) were measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). The TGF-β receptor 1 and BMP receptor 1 were inhibited by the inhibitor SB-431542 and LDN193189, respectively. Thereafter, vasohibin-1, VEGF-A, and VEGF-C expression was detected by real-time RT-PCR. We found that the expression of TGF-β1, TGF-β2, BMP-4, and BMP-7 was upregulated in TAMs cocultured with pancreatic cancer cells. Vasohibin-1, VEGF-A, and VEGF-C mRNA expression in pancreatic cancer cells was upregulated by TAMs. Vasohibin-1 expression in pancreatic cancer cells cocultured with TAMs was upregulated significantly when TGF-β receptors or BMP receptors were inhibited, but VEGF-C expression was downregulated. Therefore, Vasohibin-1 expression is regulated by the TGF-β/BMP signaling between TAMs and pancreatic cancer cells. These results might shed a new light on the antiangiogenesis therapy in the pancreatic cancer. PMID:23651239

  6. Differential Expression of Adenosine P1 Receptor ADORA1 and ADORA2A Associated with Glioma Development and Tumor-Associated Epilepsy.

    Science.gov (United States)

    Huang, Jun; Chen, Ming-Na; Du, Juan; Liu, Hao; He, Yu-Jiao; Li, Guo-Liang; Li, Shu-Yu; Liu, Wei-Ping; Long, Xiao-Yan

    2016-07-01

    Level of adenosine, an endogenous astrocyte-based neuromodulator, is primarily regulated by adenosine P1 receptors. This study assessed expression of adenosine P1 receptors, ADORA1 (adenosine A1 receptor) and ADORA2A (adenosine A2a receptor) and their association with glioma development and epilepsy in glioma patients. Expression of ADORA1/ADORA2A was assessed immunohistochemically in 65 surgically removed glioma tissue and 21 peri-tumor tissues and 8 cases of normal brain tissues obtained from hematoma patients with cerebral trauma. Immunofluorescence, Western blot, and qRT-PCR were also used to verify immunohistochemical data. Adenosine P1 receptor ADORA1 and ADORA2A proteins were localized in the cell membrane and cytoplasm and ADORA1/ADORA2A immunoreactivity was significantly stronger in glioma and peri-tumor tissues that contained infiltrating tumor cells than in normal brain tissues (p < 0.05). The World Health Organization (WHO) grade III gliomas expressed even higher level of ADORA1 and ADORA2A. Western blot and qRT-PCR confirmed immunohistochemical data. Moreover, higher levels of ADORA1 and ADORA2A expression occurred in high-grade gliomas, in which incidence of epilepsy were lower (p < 0.05). In contrast, a lower level of ADORA1/ADORA2A expression was found in peri-tumor tissues with tumor cell presence from patients with epilepsy compared to patients without epilepsy (p < 0.05). The data from the current study indicates that dysregulation in ADORA1/ADORA2A expression was associated with glioma development, whereas low level of ADORA1/ADORA2A expression could increase susceptibility of tumor-associated epilepsy. PMID:27038930

  7. 肿瘤基因信使RNA可变剪接及其应用%Alternative splicing of tumor associated genes messenger RNA and application

    Institute of Scientific and Technical Information of China (English)

    张鑫桐; 岳文涛

    2014-01-01

    可变剪接作为基因的一种修饰方式,是真核细胞表达调控过程的重要因素。它使同一蛋白质编码基因能够产生多种转录本,极大地扩展了遗传信息的应用。在人类肿瘤细胞中前体信使RN A的可变剪接扮演着重要角色,一些重要基因通过可变剪接产生不同于正常细胞中的剪接异构体。这些肿瘤特异性剪接异构体的存在导致了肿瘤的发生、发展。深入探索肿瘤相关基因的可变剪接对肿瘤的诊断、治疗具有重要意义。%As a way of gene modification,alternative splicing is an important factor of eukaryotic gene expression and regulation.It makes various transcripts from one protein-coding gene,and greatly extends the genetic information.Alternative splicing of pre-messenger RNA plays an important role in tumor cells.By alter-native splicing,some important genes can generate splicing variants different from those in normal cells.The existence of tumor-specific splicing variants leads to the occurrence and progression of tumor.Therefore,explo-ration on the alternative splicing of tumor-associated genes may be of great significance in tumor diagnosis and treatment.

  8. Visualization of the Biological Behavior of Tumor-Associated Macrophages in Living Mice with Colon Cancer Using Multimodal Optical Reporter Gene Imaging

    Directory of Open Access Journals (Sweden)

    Yun Ju Choi

    2016-03-01

    Full Text Available We sought to visualize the migration of tumor-associated macrophages (TAMs to tumor lesions and to evaluate the effects of anti-inflammatory drugs on TAM-modulated tumor progression in mice with colon cancer using a multimodal optical reporter gene system. Murine macrophage Raw264.7 cells expressing an enhanced firefly luciferase (Raw/effluc and murine colon cancer CT26 cells coexpressing Rluc and mCherry (CT26/Rluc-mCherry, CT26/RM were established. CT26/RM tumor-bearing mice received Raw/effluc via their tail veins, and combination of bioluminescence imaging (BLI and fluorescence imaging (FLI was conducted for in vivo imaging of TAMs migration and tumor progression. Dexamethasone (DEX, a potent anti-inflammatory drug, was administered intraperitoneally to tumor-bearing mice following the intravenous transfer of Raw/effluc cells. The migration of TAMs and tumor growth was monitored by serial FLI and BLI. The migration of Raw/effluc cells to tumor lesions was observed at day 1, and BLI signals were still distinct at tumor lesions on day 4. Localization of BLI signals from migrated Raw/effluc cells corresponded to that of FLI signals from CT26/RM tumors. In vivo FLI of tumors demonstrated enhanced tumor growth associated with macrophage migration to tumor lesions. Treatment with DEX inhibited the influx of Raw/effluc cells to tumor lesions and abolished the enhanced tumor growth associated with macrophage migration. These findings suggest that molecular imaging approach for TAM tracking is a valuable tool for evaluating the role of TAMs in the tumor microenvironment as well as for the development of new drugs to control TAM involvement in the modulation of tumor progression.

  9. Overexpression of interleukin-17 in tumor-associated macrophages is correlated with the differentiation and angiogenesis of laryngeal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    MENG Cui-da; ZHU Dong-dong; JIANG Xiao-dan; LI Lin; SHA Ji-chao; DONG Zhen; KONG Hong

    2012-01-01

    Background Interleukin-17 (IL-17),which exerts strong pro-inflammatory effects,has emerged as an important mediator in inflammation-associated cancer.The aim of this study was to clarify the relationship between IL-17 and tumor associated macrophages (TAMs),and the correlation of the microvessel density in the development of laryngeal squamous cell carcinoma (LSCC).Methods Histopathological observations and immunohistochemistry staining for IL-17,CD68,and CD34 were performed on 72 specimens (32 cases of LSCC,20 cases of adjacent tissues of carcinoma as controls,and 20 cases of chronic hypertrophic laryngitis).Double immunohistochemical staining was done to determine which cells expressed IL-17.Real-time quantitative PCR determined the mRNA expression of IL-17.ELISA was used to detect the expression of the serum level of IL-17 in the three groups.Results The inflammation response had increased in LSCC.Overexpression of IL-17 and CD68 protein were seen in LSCC (P <0.01).The expression of IL-17 was different between well and poorly differentiated LSCC (P <0.01).The IL-17expressing cells were mainly located in macrophages (CD68+/IL17+) as demonstrated by double immunohistochemical staining.IL-17 expression significantly correlated with high microvessel density (CD34+) in LSCC (P <0.05).Relatively higher mRNA expression levels of IL-17 were seen in LSCC compared to the controls (P <0.05).The serum expression of IL-17 was similar among the three groups (P >0.05).Conclusion IL-17 was expressed by TAMs,and IL-17 may significantly correlate to the differentiation and angiogenesis in the development of LSCC.

  10. Expression of von Hippel-Lindau tumor suppressor and tumor-associated carbonic anhydrases Ⅸ and Ⅻ in normal and neoplastic colorectal mucosa

    Institute of Scientific and Technical Information of China (English)

    Antti J. Kivela; Abdul Waheed; William S. Sly; Hannu Rajaniemi; Silvia Pastorekova; Jaromir Pastorek; Seppo Parkkila; Juha Saarnio; Tuomo J. Karttunen; Jyrki Kivela; Anna-Kaisa Parkkila; Maria Bartosova; Vojtech Mucha; Michal Novak

    2005-01-01

    AIM: To analyze possible relationships between CA Ⅸ/ CA Ⅻ and pVHL expression in normal and neoplastic colorectal mucosa.METHODS: Immunohistochemical staining of 42 tissue specimens obtained from 17 cancer patients was performed to evaluate the distribution and semi-quantitatively assess the levels of CA Ⅸ, CA Ⅻ and pVHL. VHL mRNAs from 14fresh-frozen tumors was amplified by RT-PCR and subjected to sequencing. CA9 and CA12 mRNA levels were analyzed by semi-quantitative RT-PCR in comparison with VEGF as an indicator of hypoxia that uncouples the pVHL control.RESULTS: Tumor tissues were associated with a borderline increase of CA Ⅸ staining signal and slight but significant decrease of CA Ⅻ immunoreactivity, whereas no association was found for pVHL. Sequence analysis of RT-PCR-amplified VHL mRNAs revealed no deletions/ mutations, suggesting that they were VHL-competent. We did not observe any correlation between pVHL andCA Ⅸ/CA Ⅻ proteins as well as between VEGF and CA9mRNAs, but the tumor-associated changes in mRNA levels of VEGF and CA12showed a significant inverse relationship. CONCLUSION: Our results indicate that CA9 and CA12 are regulated by different intratumoral factors and that lack of apparent relationship between the levels of CA Ⅸ/CA Ⅻ and pVHL cannot be fully assigned to uncoupling of negative regulatory function of pVHL by tumor hypoxia signified by induced VEGF transcription. The interplay between the functional pVHL and CA Ⅸ/CA Ⅻ in colorectal tumors seems rather complex and is not evident merely at the expression levels.

  11. Natural selection promotes antigenic evolvability

    NARCIS (Netherlands)

    Graves, C.J.; Ros, V.I.D.; Stevenson, B.; Sniegowski, P.D.; Brisson, D.

    2013-01-01

    The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of microbial pathogens provide

  12. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Andersen, Mads H; Ditzel, Henrik J

    2015-01-01

    /testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor...

  13. Carbohydrate – protein complex of the waste of climacoptera obtusifolia

    Directory of Open Access Journals (Sweden)

    G. Seitimova

    2013-05-01

    Full Text Available Extract from Climacoptera obtusifolia family Chenopodiaceae has antidiabetic activity. For the first time carbohydrate-protein complex of the waste from Climacoptera obtusifolia was studied. It was found that the quantity of extractive substances with 80% ethanol in aerial part – 52;6% and in the waste – 12;35%. The technique of separation of the carbohydrate-protein complex from the waste from Climacoptera obtusifolia is developed by means of classical and physical-chemical methods. The composition of carbohydrate-protein complex was identified: oligosaccharide; polysaccharide and two glycoproteins.

  14. Biosynthetic basis of incompatible histo-blood group A antigen expression

    DEFF Research Database (Denmark)

    David, L; Leitao, D; Sobrinho-Simoes, M;

    1993-01-01

    , we have screened 31 cases of gastric tumors of phenotype O for the expression of blood group A gene-defined glycosyltransferase by immunohistology on frozen sections using newly developed monoclonal antibodies to the transferases. Three cases were positive, and transferase expression was confirmed...... by enzyme analysis of extracts from the specimens. Blood group A carbohydrate antigens were also identified immunohistologically in these three cases as well as in five other cases. Thin-layer chromatography immunostaining analysis of glycolipid extracts from the three cases did not confirm the chemical...

  15. ST6GalNAc-I controls expression of sialyl-Tn antigen in gastrointestinal tissues

    DEFF Research Database (Denmark)

    Marcos, Nuno T; Bennett, Eric P; Gomes, Joana;

    2011-01-01

    Sialyl-Tn is a simple mucin-type carbohydrate antigen aberrantly expressed in gastrointestinal adenocarcinomas and in the precursor lesion intestinal metaplasia. Sialyl-Tn tumour expression is an independent indicator of poor prognosis. We have previously shown in vitro that ST6GalNAc-I and ST6Gal......-Tn biosynthesis. We developed novel monoclonal antibodies specific for ST6GalNAc-I and evaluated its expression in gastrointestinal tissues. ST6GalNAc-I was detected in normal colon mucosa co-localized with O-acetylated sialyl-Tn. Expression was largely unaltered in colorectal adenocarcinomas. In contrast, we...

  16. Application of radiation degraded carbohydrates for plants

    International Nuclear Information System (INIS)

    Radiation degraded carbohydrates such as chitosan, sodium alginate, carageenan, cellulose, pectin, etc. were applied for plant cultivation. Chitosan (poly-β -D-glucosamine) was easily degraded by irradiation and induced various kinds of biological activities such as anti-microbacterial activity, promotion of plant growth, suppression of heavy metal stress on plants, phytoalexins induction, etc. Pectic fragments obtained from degraded pectin also induced the phytoalexins such as glyceollins in soybean and pisafin in pea. The irradiated chitosan shows the higher elicitor activity for pisafin than that of pectin. For the plant growth promotion, alginate derived from brown marine algae, chitosan and ligno-cellulosic extracts show a strong activity. The hot water and ethanol extracts from EFB and sugar cane bagasse were increased by irradiation. These extracts promoted the growth of plants and suppressed the damage on barley with salt and Zn stress. The results show that the degraded polysaccharides by radiation have the potential to induce various biological activities and the products can be use for agricultural and medical fields

  17. Concepts and applications for influenza antigenic cartography

    Science.gov (United States)

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2011-01-01

    Influenza antigenic cartography projects influenza antigens into a two or three dimensional map based on immunological datasets, such as hemagglutination inhibition and microneutralization assays. A robust antigenic cartography can facilitate influenza vaccine strain selection since the antigenic map can simplify data interpretation through intuitive antigenic map. However, antigenic cartography construction is not trivial due to the challenging features embedded in the immunological data, such as data incompleteness, high noises, and low reactors. To overcome these challenges, we developed a computational method, temporal Matrix Completion-Multidimensional Scaling (MC-MDS), by adapting the low rank MC concept from the movie recommendation system in Netflix and the MDS method from geographic cartography construction. The application on H3N2 and 2009 pandemic H1N1 influenza A viruses demonstrates that temporal MC-MDS is effective and efficient in constructing influenza antigenic cartography. The web sever is available at http://sysbio.cvm.msstate.edu/AntigenMap. PMID:21761589

  18. Cancer-testis antigens and immunotherapy in the light of cancer complexity.

    Science.gov (United States)

    Grizzi, F; Mirandola, L; Qehajaj, D; Cobos, E; Figueroa, J A; Chiriva-Internati, M

    2015-03-01

    The ability of immunotherapy to evoke successful antitumor immune responses has been well documented over the past decade. Despite abundant preclinical data, it is only with the recent approval by the Food and Drug Administration (FDA) of the drugs such as sipuleucel-T and ipilimumab that immunotherapy is finally being recognized as a viable alternative to traditional therapies for treatment of various cancers. Despite the ability of immunotherapy to elicit successful antitumor immune responses, its efficacy is hindered by several factors. Among these are the paucity of tumor-associated antigens (TAA) that can be used as effective targets and the systemic toxicities that often lead to treatment interruption. Indeed, such adverse effects, which can be immunological and/or parenchymal, can be particularly severe and even fatal to some patients. A family of TAA called cancer-testis antigens (CTA) has been identified and their encoding genes have been extensively investigated. CTA expression has been demonstrated in a variety of human cancer tissues, and at least 19 CTA have been found to elicit humoral and/or cellular immune responses in cancer patients. Here we discuss how CTA and immunotherapy will most likely play a major role in the cure of cancer in the light of cancer complexity. PMID:25901859

  19. The biology of cancer testis antigens: putative function, regulation and therapeutic potential.

    Science.gov (United States)

    Fratta, Elisabetta; Coral, Sandra; Covre, Alessia; Parisi, Giulia; Colizzi, Francesca; Danielli, Riccardo; Nicolay, Hugues Jean Marie; Sigalotti, Luca; Maio, Michele

    2011-04-01

    Cancer testis antigens (CTA) are a large family of tumor-associated antigens expressed in human tumors of different histological origin, but not in normal tissues except for testis and placenta. This tumor-restricted pattern of expression, together with their strong in vivo immunogenicity, identified CTA as ideal targets for tumor-specific immunotherapeutic approaches, and prompted the development of several clinical trials of CTA-based vaccine therapy. Driven by this practical clinical interest, a more detailed characterization of CTA biology has been recently undertaken. So far, at least 70 families of CTA, globally accounting for about 140 members, have been identified. Most of these CTA are expressed during spermatogenesis, but their function is still largely unknown. Epigenetic events, particularly DNA methylation, appear to be the primary mechanism regulating CTA expression in both normal and transformed cells, as well as in cancer stem cells. In view of the growing interest in CTA biology, the aim of this review is to provide the most recent information on their expression, regulation and function, together with a brief summary of the major clinical trials involving CTA as therapeutic agents. The pharmacologic modulation of CTA expression profiles on neoplastic cells by DNA hypomethylating drugs will also be discussed as a feasible approach to design new combination therapies potentially able to improve the clinical efficacy of currently adopted CTA-based immunotherapeutic regimens in cancer patients.

  20. Genome Scale Identification of Treponema pallidum Antigens

    OpenAIRE

    McKevitt, Matthew; Brinkman, Mary Beth; McLoughlin, Melanie; Perez, Carla; Howell, Jerrilyn K.; Weinstock, George M.; Norris, Steven J; Palzkill, Timothy

    2005-01-01

    Antibody responses for 882 of the 1,039 proteins in the proteome of Treponema pallidum were examined. Sera collected from infected rabbits were used to systematically identify 106 antigenic proteins, including 22 previously identified antigens and 84 novel antigens. Additionally, sera collected from rabbits throughout the course of infection demonstrated a progression in the breadth and intensity of humoral immunoreactivity against a representative panel of T. pallidum antigens.

  1. Synthesis of Heterocylic Compounds of Biological Interest from Carbohydrate Derivatives

    OpenAIRE

    M. F. Martinez Esperón; Fascio, M. L.; N. B. D’Accorso

    2000-01-01

    The synthesis of some isoxazolic compounds from carbohydrate derivatives is described. These products are obtained by 1,3-dipolar cycloaddition reaction and their functionalization leads to derivatives with potential biological activities.

  2. The role of carbohydrate in dietary prescription for weight loss

    DEFF Research Database (Denmark)

    Astrup, Arne

    to be shown whether a low-glycemic index diet provides benefits beyond this. Low-carbohydrate diets may be an option for inducing weight loss in obese patients, but a very low intake of carbohydrate-rich foods is not commensurate with a healthy and palatable diet in the long term. However, there is evidence......The optimal diet for prevention of weight gain, obesity, metabolic syndrome, and type 2 diabetes is fat-reduced, fibre-rich, high in lowenergy density carbohydrates (fruit, vegetables, and whole grain products), and intake of energy-containing drinks is restricted. The reduction of the total fat...... that increasing the protein content of the diet from 15% up to 20–30%, at the expense of carbohydrate, increases the satiating effect of the diet, and induces a spontaneous weight loss, and this could turn out to be a preferred option for patients with metabolic syndrome and type 2 diabetes....

  3. What I Need to Know about Carbohydrate Counting and Diabetes

    Science.gov (United States)

    ... zucchini. Foods that do not contain carbohydrates include meat, fish, and poultry; most types of cheese; nuts; ... Training & Career Development Research at NIDDK Research Resources Technology Advancement & Transfer Meetings & Events Health Information Health Topics ...

  4. Carbohydrate biomarkers for future disease detection and treatment

    Institute of Scientific and Technical Information of China (English)

    REID; Suazette

    2010-01-01

    Carbohydrates are considered as one of the most important classes of biomarkers for cell types,disease states,protein functions,and developmental states.Carbohydrate"binders"that can specifically recognize a carbohydrate biomarker can be used for developing novel types of site specific delivery methods and imaging agents.In this review,we present selected examples of important carbohydrate biomarkers and how they can be targeted for the development of therapeutic and diagnostic agents.Examples are arranged based on disease categories including(1) infectious diseases,(2) cancer,(3) inflammation and immune responses,(4) signal transduction,(5) stem cell transformation,(6) embryo development,and(7) cardiovascular diseases,though some issues cross therapeutic boundaries.

  5. Research progress in tumor-associated lipids and lipidomics%肿瘤相关脂类及脂类组学的研究进展

    Institute of Scientific and Technical Information of China (English)

    范左栩; 马小琼; 詹仁雅

    2012-01-01

    Lipidomics, a newly emerged branch of metabolomics, is aimed to systemically study the characters of lipid molecular species in organisms and their roles in regulating protein and gene expression. Lipids play diverse biological roles in organisms; including energy storage, signal traasduclion and apoptosis. Owning to the rapid progression of novel analytical technique, especially the application of mass spectrometry. lipid examination can be done rapidly and accurately in a high throughput manner. Many studies have demonstrated that abnormal metabolism of lipids is closely related to the development and progression of tumors. Application of lipidomics technique can reveal the changes of tumor-associated lipid and identify the abnormal metabolic pathways. Also, lipidomics has a promising future in recognition of lipid-based tumor markers, early diagnosis of tumors and the discovery of antineoplastic drug targets. In this article, we reviewed the recent progress in the above-mentioned areas.%脂类组学是一门新兴的代谢组学的分支学科,旨在系统研究生物体内所有脂类分子的特性,以及它们在蛋白质表达和基因表达调节过程中的作用.脂类参与调节生物体的众多生理过程,包括能量存储、信号转导、细胞凋亡等,随着新的分析技术的发展,特别是质谱技术的应用和发展,脂类的测定得以快速、精确和高通量地进行.大量研究表明,脂类代谢异常与肿瘤的发生发展有着密切联系,脂类组学技术的应用能揭示与肿瘤相关的脂类变化,找到其异常的代谢通路,并在肿瘤脂类生物标志物的识别、肿瘤早期诊断和抗肿瘤药物靶点的发现等方面展现出广泛的应用前景.本文就上述研究的近期进展作简要综述.

  6. Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization

    International Nuclear Information System (INIS)

    Tumor-associated macrophages (TAM) play an important role in tumor microenvironment. Particularly, M2 macrophages contribute to tumor progression, depending on the expression of NF-κB. Tumor-derived exosomes can modulate tumor microenvironment by transferring miRNAs to immune cells. Epigallocatechin gallate (EGCG) has well known anti-tumor effects; however, no data are available on the influence of EGCG on communication with cancer cells and TAM. Murine breast cancer cell lines, 4T1, was used for in vivo and ex vivo studies. Exosome was extracted from EGCG-treated 4T1 cells, and the change of miRNAs was screened using microarray. Tumor cells or TAM isolated from murine tumor graft were incubated with exosomes derived from EGCG-treated and/or miR-16 inhibitor-transfected 4T1 cells. Chemokines for monocytes (CSF-1 and CCL-2), cytokines both with high (IL-6 and TGF-β) and low (TNF-α) expression in M2 macrophages, and molecules in NF-κB pathway (IKKα and Iκ-B) were evaluated by RT-qPCR or western blot. EGCG suppressed tumor growth in murine breast cancer model, which was associated with decreased TAM and M2 macrophage infiltration. Expression of chemokine for monocytes (CSF-1 and CCL-2) were low in tumor cells from EGCG-treated mice, and cytokines of TAM was skewed from M2- into M1-like phenotype by EGCG as evidenced by decreased IL-6 and TGF-β and increased TNF-α. Ex vivo incubation of isolated tumor cells with EGCG inhibited the CSF-1 and CCL-2 expression. Ex vivo incubation of TAM with exosomes from EGCG-treated 4T1 cells led to IKKα suppression and concomitant I-κB accumulation; increase of IL-6 and TGF-β; and, decrease of TNF-α. EGCG up-regulated miR-16 in 4T1 cells and in the exosomes. Treatment of tumor cells or TAM with exosomes derived from EGCG-treated and miR-16-knock-downed 4T1 cells restored the above effects on chemokines, cytokines, and NF-κB pathway elicited by EGCG-treated exosomes. Our data demonstrate that EGCG up-regulates miR-16 in

  7. Carbohydrate catabolic diversity of bifidobacteria and lactobacilli of human origin.

    Science.gov (United States)

    McLaughlin, Heather P; Motherway, Mary O'Connell; Lakshminarayanan, Bhuvaneswari; Stanton, Catherine; Paul Ross, R; Brulc, Jennifer; Menon, Ravi; O'Toole, Paul W; van Sinderen, Douwe

    2015-06-16

    Because increased proportions of particular commensal bacteria such as bifidobacteria and lactobacilli have been linked to human health through a variety of mechanisms, there is corresponding interest in identifying carbohydrates that promote growth and metabolic activity of these bacteria. We evaluated the ability of 20 carbohydrates, including several commercially available carbohydrates that are sold as prebiotic ingredients, to support growth of 32 human-derived isolates belonging to the genera Bifidobacterium and Lactobacillus, including those isolated from healthy elderly subjects. In general, bifidobacterial strains were shown to display more diverse carbohydrate utilization profiles compared to the tested Lactobacillus species, with several bifidobacterial strains capable of metabolizing xylo-oligosaccharide (XOS), arabinoxylan, maltodextrin, galactan and carbohydrates containing fructo-oligosaccharide (FOS) components. In contrast, maltodextrin, galactan, arabinogalactan and galactomannan did not support robust growth (≥0.8 OD600 nm) of any of the Lactobacillus strains assessed. Carbohydrate fermentation was variable among strains tested of the same species for both genera. This study advances our knowledge of polysaccharide utilization by human gut commensals, and provides information for the rational design of selective prebiotic food ingredients. PMID:25817019

  8. Magnesium and disturbances in carbohydrate metabolism.

    Science.gov (United States)

    Mooren, Frank C

    2015-09-01

    Magnesium is actively involved in a number of metabolic reactions as an important co-factor, with special emphasis on carbohydrate metabolism. After a brief overview of the regulation of intra- and extracellular magnesium, the present review first describes the regulatory role of magnesium in important metabolic pathways involved in energy metabolism and glycaemic control. Next the clinical significance of hypomagnesaemic conditions with regard to the management of glucose in prediabetic stages, such as insulin resistance/impaired glucose tolerance and in type 2 diabetes mellitus are characterized. Cross-sectional as well as longitudinal studies suggest that a reduced dietary magnesium intake serves as a risk factor for the incidence of both impaired glucose regulation and type 2 diabetes. Mechanisms that might be responsible for diabetes-associated hypomagnesaemia are discussed. Furthermore, the role of hypomagnesaemia in the development and progression of chronic diabetic complications are addressed. Finally, the available literature on the effects of magnesium supplementation on glycaemic control parameters during prediabetic conditions (preventive approach) as well as type 2 diabetes mellitus (therapeutic approach) are reviewed systematically. There is considerable evidence that chronic magnesium supplementation may delay the progression from impaired glucose regulation to type 2 diabetes; however, the effects of oral magnesium supplementation as an adjunct therapy for type 2 diabetes are quite heterogeneous with respect to the various measures of glycaemic control. The results of this review suggest a requirement for critical consideration of the pros and cons of magnesium replacement therapy, based on variables such as magnesium status, stage of disease and glycaemic control.

  9. Cause of impaired carbohydrate metabolism in hyperthyroidism

    International Nuclear Information System (INIS)

    Hyperthyroidism (HT) affects glucose metabolism in various ways. The role of insulin, glucagon and growth-hormone (GH) was determined. After glucose loading the insulin response is weaker in HT than in euthyroid subjects. Enhanced degradation of insulin has been reported. It is suggested that in HT the serum insulin concentration declines at a slightly accelerated rate. In HT the deranged carbohydrate metabolism might be a consequence of altered tissue sensitivity to insulin. To elucidate this problem insulin receptors on erythrocytes obtained from hyperthyroid women were investigated. The maximal specific binding of 125I-insulin to RBC of hyperthyroid patients was decreased and the analysis refers to a decreased receptor concentration in RBC. The nature of glucagon secretion and its influence on glucose metabolism in HT was investigated. The basal plasma glucagon is elevated in hyperthyroid patients. The suppression of glucagon secretion induced by an oral glucose loading was of significantly lesser degree in hyperthyroid patients than in controls. Applying the erythrocyte receptor assay a decreased specific binding of 125I-glucagon to RBC of hyperthyroid patients has been found and data indicate a significantly less glucagon receptor concentration in thyrotoxicosis. Physiological elevations of serum GH levels led to a significant impairment of glucose metabolism. Beside the GH-RH and somatostatin, the dopaminergic neurotransmitter system participates in the regulation of GH secretion too. It has been demonstrated that after administration of the dopamine agonist l-dopa the GH response was weaker in HT than in controls. This indicates that in thyrotoxicosis the GH secretion can not be stimulated in such a degree as in euthyroidism. (author)

  10. Using Carbohydrate Interaction Assays to Reveal Novel Binding Sites in Carbohydrate Active Enzymes.

    Science.gov (United States)

    Cockburn, Darrell; Wilkens, Casper; Dilokpimol, Adiphol; Nakai, Hiroyuki; Lewińska, Anna; Abou Hachem, Maher; Svensson, Birte

    2016-01-01

    Carbohydrate active enzymes often contain auxiliary binding sites located either on independent domains termed carbohydrate binding modules (CBMs) or as so-called surface binding sites (SBSs) on the catalytic module at a certain distance from the active site. The SBSs are usually critical for the activity of their cognate enzyme, though they are not readily detected in the sequence of a protein, but normally require a crystal structure of a complex for their identification. A variety of methods, including affinity electrophoresis (AE), insoluble polysaccharide pulldown (IPP) and surface plasmon resonance (SPR) have been used to study auxiliary binding sites. These techniques are complementary as AE allows monitoring of binding to soluble polysaccharides, IPP to insoluble polysaccharides and SPR to oligosaccharides. Here we show that these methods are useful not only for analyzing known binding sites, but also for identifying new ones, even without structural data available. We further verify the chosen assays discriminate between known SBS/CBM containing enzymes and negative controls. Altogether 35 enzymes are screened for the presence of SBSs or CBMs and several novel binding sites are identified, including the first SBS ever reported in a cellulase. This work demonstrates that combinations of these methods can be used as a part of routine enzyme characterization to identify new binding sites and advance the study of SBSs and CBMs, allowing them to be detected in the absence of structural data. PMID:27504624

  11. Antigen Export Reduces Antigen Presentation and Limits T Cell Control of M. tuberculosis.

    Science.gov (United States)

    Srivastava, Smita; Grace, Patricia S; Ernst, Joel D

    2016-01-13

    Persistence of Mycobacterium tuberculosis results from bacterial strategies that manipulate host adaptive immune responses. Infected dendritic cells (DCs) transport M. tuberculosis to local lymph nodes but activate CD4 T cells poorly, suggesting bacterial manipulation of antigen presentation. However, M. tuberculosis antigens are also exported from infected DCs and taken up and presented by uninfected DCs, possibly overcoming this blockade of antigen presentation by infected cells. Here we show that the first stage of this antigen transfer, antigen export, benefits M. tuberculosis by diverting bacterial proteins from the antigen presentation pathway. Kinesin-2 is required for antigen export and depletion of this microtubule-based motor increases activation of antigen-specific CD4 T cells by infected cells and improves control of intracellular infection. Thus, although antigen transfer enables presentation by bystander cells, it does not compensate for reduced antigen presentation by infected cells and represents a bacterial strategy for CD4 T cell evasion.

  12. Assessing the Impacts of Low Carbohydrate Related Health Information on the Market Demand for US Vegetables

    OpenAIRE

    Paudel, Laxmi; Adhikari, Murali; Houston, Jack E.

    2005-01-01

    An Almost Ideal Demand System was estimated to examine the impacts of low carbohydrate information on the market demand for US vegetables. Analysis was extended to examine the performance of alternative carbohydrate information indexes. Study shows significant robust impacts of low carbohydrate information across all included vegetables. Results favor the general and weighted carbohydrate information index.

  13. Antigenic Variation in Plasmodium falciparum.

    Science.gov (United States)

    Petter, Michaela; Duffy, Michael F

    2015-01-01

    Plasmodium falciparum is the protozoan parasite that causes most malaria-associated morbidity and mortality in humans with over 500,000 deaths annually. The disease symptoms are associated with repeated cycles of invasion and asexual multiplication inside red blood cells of the parasite. Partial, non-sterile immunity to P. falciparum malaria develops only after repeated infections and continuous exposure. The successful evasion of the human immune system relies on the large repertoire of antigenically diverse parasite proteins displayed on the red blood cell surface and on the merozoite membrane where they are exposed to the human immune system. Expression switching of these polymorphic proteins between asexual parasite generations provides an efficient mechanism to adapt to the changing environment in the host and to maintain chronic infection. This chapter discusses antigenic diversity and variation in the malaria parasite and our current understanding of the molecular mechanisms that direct the expression of these proteins. PMID:26537377

  14. The Interplay of Antigen Affinity, Internalization, and Pharmacokinetics on CD44-Positive Tumor Targeting of Monoclonal Antibodies.

    Science.gov (United States)

    Glatt, Dylan M; Beckford Vera, Denis R; Parrott, Matthew C; Luft, J Christopher; Benhabbour, S Rahima; Mumper, Russell J

    2016-06-01

    Monoclonal antibodies (mAbs) offer promise as effective tumor targeting and drug delivery agents for cancer therapy. However, comparative biological and clinical characteristics of mAbs targeting the same tumor-associated antigen (TAA) often differ widely. This study examined the characteristics of mAbs that impact tumor targeting using a panel of mAb clones specific to the cancer-associated cell-surface receptor and cancer stem cell marker CD44. CD44 mAbs were screened for cell-surface binding, antigen affinity, internalization, and CD44-mediated tumor uptake by CD44-positive A549 cells. It was hypothesized that high-affinity, rapidly internalizing CD44 mAbs would result in high tumor uptake and prolonged tumor retention. Although high-affinity clones rapidly bound and were internalized by A549 cells in vitro, an intermediate-affinity clone demonstrated significantly greater tumor uptake and retention than high-affinity clones in vivo. Systemic exposure, rather than high antigen affinity or rapid internalization, best associated with tumor targeting of CD44 mAbs in A549 tumor-bearing mice. PMID:27079967

  15. Polymeric Structure and Host Toll-like Receptor 4 Dictate Immunogenicity of NY-ESO-1 Antigen in Vivo*

    Science.gov (United States)

    Liu, Yanan; Tian, Xiaoli; Leitner, Wolfgang W.; Aldridge, Michael E.; Zheng, Junying; Yu, Zhiya; Restifo, Nicholas P.; Weiss, Richard; Scheiblhofer, Sandra; Xie, Chong; Sun, Ren; Cheng, Genhong; Zeng, Gang

    2011-01-01

    In search of intrinsic factors that contribute to the distinctively strong immunogenicity of a non-mutated cancer/testis antigen, we found that NY-ESO-1 forms polymeric structures through disulfide bonds. NY-ESO-1 binding to immature dendritic cells was dependent on its polymeric structure and involved Toll-like receptor-4 (TLR4) on the surface of immature dendritic cells in mouse and human. Gene gun-delivered plasmid encoding the wild-type NY-ESO-1 readily induced T cell-dependent antibody (Ab) responses in wild-type C57BL/10 mice but not TLR4-knock-out C57BL/10ScNJ mice. Disrupting polymeric structures of NY-ESO-1 by cysteine-to-serine (Cys-to-Ser) substitutions lead to diminished immunogenicity and altered TLR4-dependence in the induced Ab response. To demonstrate its adjuvant effect, NY-ESO-1 was fused with a major mugwort pollen allergen Art v 1 and a tumor-associated antigen, carbonic anhydrase 9. Plasmid DNA vaccines encoding the fusion genes generated robust immune responses against otherwise non-immunogenic targets in mice. Polymeric structure and TLR4 may play important roles in rendering NY-ESO-1 immunogenic and thus serve as a potent molecular adjuvant. NY-ESO-1 thus represents the first example of a cancer/testis antigen that is a also damage-associated molecular pattern. PMID:21900253

  16. Polymeric structure and host Toll-like receptor 4 dictate immunogenicity of NY-ESO-1 antigen in vivo.

    Science.gov (United States)

    Liu, Yanan; Tian, Xiaoli; Leitner, Wolfgang W; Aldridge, Michael E; Zheng, Junying; Yu, Zhiya; Restifo, Nicholas P; Weiss, Richard; Scheiblhofer, Sandra; Xie, Chong; Sun, Ren; Cheng, Genhong; Zeng, Gang

    2011-10-28

    In search of intrinsic factors that contribute to the distinctively strong immunogenicity of a non-mutated cancer/testis antigen, we found that NY-ESO-1 forms polymeric structures through disulfide bonds. NY-ESO-1 binding to immature dendritic cells was dependent on its polymeric structure and involved Toll-like receptor-4 (TLR4) on the surface of immature dendritic cells in mouse and human. Gene gun-delivered plasmid encoding the wild-type NY-ESO-1 readily induced T cell-dependent antibody (Ab) responses in wild-type C57BL/10 mice but not TLR4-knock-out C57BL/10ScNJ mice. Disrupting polymeric structures of NY-ESO-1 by cysteine-to-serine (Cys-to-Ser) substitutions lead to diminished immunogenicity and altered TLR4-dependence in the induced Ab response. To demonstrate its adjuvant effect, NY-ESO-1 was fused with a major mugwort pollen allergen Art v 1 and a tumor-associated antigen, carbonic anhydrase 9. Plasmid DNA vaccines encoding the fusion genes generated robust immune responses against otherwise non-immunogenic targets in mice. Polymeric structure and TLR4 may play important roles in rendering NY-ESO-1 immunogenic and thus serve as a potent molecular adjuvant. NY-ESO-1 thus represents the first example of a cancer/testis antigen that is a also damage-associated molecular pattern.

  17. [HLA antigens in juvenile rheumatoid arthritis].

    Science.gov (United States)

    Rumba, I V; Sochnev, A M; Kukaĭne, E M; Burshteĭn, A M; Benevolenskaia, L I

    1990-01-01

    Antigens of I class HLA system (locus A and B) were investigated in 67 patients of Latvian nationality suffering from juvenile rheumatoid arthritis (JRA). Associations of HLA antigens with juvenile rheumatoid arthritis partially coincided with the ones revealed earlier. Typing established an increased incidence of antigen B27 (p less than 0.01) and gaplotype A2, B40 (p less than 0.01). Antigen B15 possessed a protective action with respect to JRA. Interlocus combinations demonstrated a closer association with the disease than a single antigen. The authors also revealed markers of various clinico-anatomical variants of JRA.

  18. Modified carbohydrate-chitosan compounds, methods of making the same and methods of using the same

    Energy Technology Data Exchange (ETDEWEB)

    Venditti, Richard A; Pawlak, Joel J; Salam, Abdus; El-Tahlawy, Khaled Fathy

    2015-03-10

    Compositions of matter are provided that include chitosan and a modified carbohydrate. The modified carbohydrate includes a carbohydrate component and a cross linking agent. The modified carbohydrate has increased carboxyl content as compared to an unmodified counterpart carbohydrate. A carboxyl group of the modified carbohydrate is covalently bonded with an amino group of chitosan. The compositions of matter provided herein may include cross linked starch citrate-chitosan and cross linked hemicellulose citrate-chitosan, including foams thereof. These compositions yield excellent absorbency and metal chelation properties. Methods of making cross linked modified carbohydrate-chitosan compounds are also provided.

  19. Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling and activation

    DEFF Research Database (Denmark)

    Napoletano, Chiara; Zizzari, Ilaria G; Rughetti, Aurelia;

    2012-01-01

    Dendritic cells (DCs) sense the microenvironment through several types of receptors recognizing pathogen-associated molecular patterns. In particular, C-type lectins, expressed by distinct subsets of DCs, recognize and internalize specific carbohydrate antigen in a Ca(2+) -dependent manner......NAc or Tn)-carrying tumor-associated antigens to improve DC performance. MGL expressed by ex vivo-generated iDCs from healthy donors was engaged by a 60-mer MUC1(9Tn) -glycopeptide as a Tn-carrying tumor-associated antigen, and an anti-MGL antibody, as a specific MGL binder. We demonstrated that MGL...

  20. A nonself sugar mimic of the HIV glycan shield shows enhanced antigenicity

    Energy Technology Data Exchange (ETDEWEB)

    Doores, Katie J.; Fulton, Zara; Hong, Vu; Patel, Mitul K.; Scanlan, Christopher N.; Wormald, Mark R.; Finn, M.G.; Burton, Dennis R.; Wilson, Ian A.; Davis, Benjamin G. (Scripps); (Oxford)

    2011-08-24

    Antibody 2G12 uniquely neutralizes a broad range of HIV-1 isolates by binding the high-mannose glycans on the HIV-1 surface glycoprotein, gp120. Antigens that resemble these natural epitopes of 2G12 would be highly desirable components for an HIV-1 vaccine. However, host-produced (self)-carbohydrate motifs have been unsuccessful so far at eliciting 2G12-like antibodies that cross-react with gp120. Based on the surprising observation that 2G12 binds nonproteinaceous monosaccharide D-fructose with higher affinity than D-mannose, we show here that a designed set of nonself, synthetic monosaccharides are potent antigens. When introduced to the terminus of the D1 arm of protein glycans recognized by 2G12, their antigenicity is significantly enhanced. Logical variation of these unnatural sugars pinpointed key modifications, and the molecular basis of this increased antigenicity was elucidated using high-resolution crystallographic analyses. Virus-like particle protein conjugates containing such nonself glycans are bound more tightly by 2G12. As immunogens they elicit higher titers of antibodies than those immunogenic conjugates containing the self D1 glycan motif. These antibodies generated from nonself immunogens also cross-react with this self motif, which is found in the glycan shield, when it is presented in a range of different conjugates and glycans. However, these antibodies did not bind this glycan motif when present on gp120.

  1. Multivalent display of minimal Clostridium difficile glycan epitopes mimics antigenic properties of larger glycans

    Science.gov (United States)

    Broecker, Felix; Hanske, Jonas; Martin, Christopher E.; Baek, Ju Yuel; Wahlbrink, Annette; Wojcik, Felix; Hartmann, Laura; Rademacher, Christoph; Anish, Chakkumkal; Seeberger, Peter H.

    2016-01-01

    Synthetic cell-surface glycans are promising vaccine candidates against Clostridium difficile. The complexity of large, highly antigenic and immunogenic glycans is a synthetic challenge. Less complex antigens providing similar immune responses are desirable for vaccine development. Based on molecular-level glycan–antibody interaction analyses, we here demonstrate that the C. difficile surface polysaccharide-I (PS-I) can be resembled by multivalent display of minimal disaccharide epitopes on a synthetic scaffold that does not participate in binding. We show that antibody avidity as a measure of antigenicity increases by about five orders of magnitude when disaccharides are compared with constructs containing five disaccharides. The synthetic, pentavalent vaccine candidate containing a peptide T-cell epitope elicits weak but highly specific antibody responses to larger PS-I glycans in mice. This study highlights the potential of multivalently displaying small oligosaccharides to achieve antigenicity characteristic of larger glycans. The approach may result in more cost-efficient carbohydrate vaccines with reduced synthetic effort. PMID:27091615

  2. Stable solid-phase Rh antigen.

    Science.gov (United States)

    Yared, M A; Moise, K J; Rodkey, L S

    1997-12-01

    Numerous investigators have attempted to isolate the Rh antigens in a stable, immunologically reactive form since the discovery of the Rh system over 56 years ago. We report here a successful and reproducible approach to solubilizing and adsorbing the human Rh antigen(s) to a solid-phase matrix in an antigenically active form. Similar results were obtained with rabbit A/D/F red blood cell antigens. The antigen preparation was made by dissolution of the red blood cell membrane lipid followed by fragmentation of the residual cytoskeleton in an EDTA solution at low ionic strength. The antigenic activity of the soluble preparations was labile in standard buffers but was stable in zwitterionic buffers for extended periods of time. Further studies showed that the antigenic activity of these preparations was enhanced, as was their affinity for plastic surfaces, in the presence of acidic zwitterionic buffers. Adherence to plastic surfaces at low pH maintained antigenic reactivity and specificity for antibody was retained. The data show that this approach yields a stable form of antigenically active human Rh D antigen that could be used in a red blood cell-free assay for quantitative analysis of Rh D antibody and for Rh D antibody immunoadsorption and purification.

  3. A structural model for binding of the serine-rich repeat adhesin GspB to host carbohydrate receptors.

    Directory of Open Access Journals (Sweden)

    Tasia M Pyburn

    2011-07-01

    Full Text Available GspB is a serine-rich repeat (SRR adhesin of Streptococcus gordonii that mediates binding of this organism to human platelets via its interaction with sialyl-T antigen on the receptor GPIbα. This interaction appears to be a major virulence determinant in the pathogenesis of infective endocarditis. To address the mechanism by which GspB recognizes its carbohydrate ligand, we determined the high-resolution x-ray crystal structure of the GspB binding region (GspB(BR, both alone and in complex with a disaccharide precursor to sialyl-T antigen. Analysis of the GspB(BR structure revealed that it is comprised of three independently folded subdomains or modules: 1 an Ig-fold resembling a CnaA domain from prokaryotic pathogens; 2 a second Ig-fold resembling the binding region of mammalian Siglecs; 3 a subdomain of unique fold. The disaccharide was found to bind in a pocket within the Siglec subdomain, but at a site distinct from that observed in mammalian Siglecs. Confirming the biological relevance of this binding pocket, we produced three isogenic variants of S. gordonii, each containing a single point mutation of a residue lining this binding pocket. These variants have reduced binding to carbohydrates of GPIbα. Further examination of purified GspB(BR-R484E showed reduced binding to sialyl-T antigen while S. gordonii harboring this mutation did not efficiently bind platelets and showed a significant reduction in virulence, as measured by an animal model of endocarditis. Analysis of other SRR proteins revealed that the predicted binding regions of these adhesins also had a modular organization, with those known to bind carbohydrate receptors having modules homologous to the Siglec and Unique subdomains of GspB(BR. This suggests that the binding specificity of the SRR family of adhesins is determined by the type and organization of discrete modules within the binding domains, which may affect the tropism of organisms for different tissues.

  4. A Structural Model for Binding of the Serine-Rich Repeat Adhesin GspB to Host Carbohydrate Receptors

    Energy Technology Data Exchange (ETDEWEB)

    Pyburn, Tasia M.; Bensing, Barbara A.; Xiong, Yan Q.; Melancon, Bruce J.; Tomasiak, Thomas M.; Ward, Nicholas J.; Yankovskaya, Victoria; Oliver, Kevin M.; Cecchini, Gary; Sulikowski, Gary A.; Tyska, Matthew J.; Sullam, Paul M.; Iverson, T.M. (VA); (UCLA); (Vanderbilt); (UCSF)

    2014-10-02

    GspB is a serine-rich repeat (SRR) adhesin of Streptococcus gordonii that mediates binding of this organism to human platelets via its interaction with sialyl-T antigen on the receptor GPIb{alpha}. This interaction appears to be a major virulence determinant in the pathogenesis of infective endocarditis. To address the mechanism by which GspB recognizes its carbohydrate ligand, we determined the high-resolution x-ray crystal structure of the GspB binding region (GspB{sub BR}), both alone and in complex with a disaccharide precursor to sialyl-T antigen. Analysis of the GspB{sub BR} structure revealed that it is comprised of three independently folded subdomains or modules: (1) an Ig-fold resembling a CnaA domain from prokaryotic pathogens; (2) a second Ig-fold resembling the binding region of mammalian Siglecs; (3) a subdomain of unique fold. The disaccharide was found to bind in a pocket within the Siglec subdomain, but at a site distinct from that observed in mammalian Siglecs. Confirming the biological relevance of this binding pocket, we produced three isogenic variants of S. gordonii, each containing a single point mutation of a residue lining this binding pocket. These variants have reduced binding to carbohydrates of GPIb{alpha}. Further examination of purified GspB{sub BR}-R484E showed reduced binding to sialyl-T antigen while S. gordonii harboring this mutation did not efficiently bind platelets and showed a significant reduction in virulence, as measured by an animal model of endocarditis. Analysis of other SRR proteins revealed that the predicted binding regions of these adhesins also had a modular organization, with those known to bind carbohydrate receptors having modules homologous to the Siglec and Unique subdomains of GspBBR. This suggests that the binding specificity of the SRR family of adhesins is determined by the type and organization of discrete modules within the binding domains, which may affect the tropism of organisms for different tissues.

  5. Predicting water-soluble carbohydrates and ethanol-soluble carbohydrates in cool-season grasses with near-infrared reflectance spectroscopy

    Science.gov (United States)

    Grazing animals may require a high or low total nonstructural carbohydrate diet for optimal health and production. Understanding how nonstructural carbohydrates fluctuate in Kentucky pastures and being able to quantify and monitor nonstructural carbohydrates in a timely manner will greatly aid in m...

  6. Promiscuity of the Euonymus Carbohydrate-Binding Domain

    Directory of Open Access Journals (Sweden)

    Els J.M. Van Damme

    2012-10-01

    Full Text Available Plants synthesize small amounts of carbohydrate-binding proteins on exposure to stress. For example, on exposure to drought, high salt, wounding and by treatment with some plant hormones or by pathogen attack. In contrast to the ‘classical’ plant lectins that are mostly located in the vacuolar compartment, this new class of inducible lectins is present in the cytoplasm and in the nucleus. Taking into account that any physiological role of plant lectins most likely relies on their specific carbohydrate-binding activity and specificity, the discovery of these stress-related lectins provides strong evidence for the importance of protein-carbohydrate-interactions in plant cells. Hitherto, six families of such nucleocytoplasmic lectins have been identified in plants. This review will focus on the nucleocytoplasmic lectins with one or more Euonymus lectin (EUL domain(s. The carbohydrate-binding specificity of EUL proteins from a monocot, a dicot and a lower plant has been compared. Furthermore, modeling of the different EUL domains revealed a similar ß-trefoil fold consisting of three bundles of ß-sheet organized around a pseudo three-fold symmetry axis. Despite the sequence similarity and the conserved amino acids in the binding site, glycan array analyses showed that the EUL domain has a promiscuous carbohydrate-binding site capable of accommodating high mannose N-glycans, blood group B related structures and galactosylated epitopes.

  7. Interaction of carbohydrates with alcohol dehydrogenase: Effect on enzyme activity.

    Science.gov (United States)

    Jadhav, Swati B; Bankar, Sandip B; Granström, Tom; Ojamo, Heikki; Singhal, Rekha S; Survase, Shrikant A

    2015-09-01

    Alcohol dehydrogenase was covalently conjugated with three different oxidized carbohydrates i.e., glucose, starch and pectin. All the carbohydrates inhibited the enzyme. The inhibition was studied with respect to the inhibition rate constant, involvement of thiol groups in the binding, and structural changes in the enzyme. The enzyme activity decreased to half of its original activity at the concentration of 2 mg/mL of pectin, 4 mg/mL of glucose and 10 mg/mL of starch within 10 min at pH 7. This study showed oxidized pectin to be a potent inhibitor of alcohol dehydrogenase followed by glucose and starch. Along with the aldehyde-amino group interaction, thiol groups were also involved in the binding between alcohol dehydrogenase and carbohydrates. The structural changes occurring on binding of alcohol dehydrogenase with oxidized carbohydrates was also confirmed by fluorescence spectrophotometry. Oxidized carbohydrates could thus be used as potential inhibitors of alcohol dehydrogenase.

  8. Pharmaceutical, cosmeceutical, and traditional applications of marine carbohydrates.

    Science.gov (United States)

    Ahmed, Abdul Bakrudeen Ali; Adel, Mohaddeseh; Karimi, Pegah; Peidayesh, Mahvash

    2014-01-01

    Marine carbohydrates are most important organic molecules made by photosynthetic organisms. It is very essential for humankind: the role in being an energy source for the organism and they are considered as an important dissolve organic compound (DOC) in marine environment's sediments. Carbohydrates found in different marine environments in different concentrations. Polysaccharides of carbohydrates play an important role in various fields such as pharmaceutical, food production, cosmeceutical, and so on. Marine organisms are good resources of nutrients, and they are rich carbohydrate in sulfated polysaccharide. Seaweeds (marine microalgae) are used in different pharmaceutical industries, especially in pharmaceutical compound production. Seaweeds have a significant amount of sulfated polysaccharides, which are used in cosmeceutical industry, besides based on the biological applications. Since then, traditional people, cosmetics products, and pharmaceutical applications consider many types of seaweed as an important organism used in food process. Sulfated polysaccharides containing seaweed have potential uses in the blood coagulation system, antiviral activity, antioxidant activity, anticancer activity, immunomodulating activity, antilipidepic activity, etc. Some species of marine organisms are rich in polysaccharides such as sulfated galactans. Various polysaccharides such as agar and alginates, which are extracted from marine organisms, have several applications in food production and cosmeceutical industries. Due to their high health benefits, compound-derived extracts of marine polysaccharides have various applications and traditional people were using them since long time ago. In the future, much attention is supposed to be paid to unraveling the structural, compositional, and sequential properties of marine carbohydrate as well.

  9. Correlation between carbohydrate structures on the envelope glycoprotein gp120 of HIV-1 and HIV-2 and syncytium inhibition with lectins

    DEFF Research Database (Denmark)

    Hansen, J E; Nielsen, C M; Nielsen, C;

    1989-01-01

    The binding of 13 different lectins to gp120 partially purified from two HIV-1 isolates and one HIV-2 isolate was studied by in situ staining on electrophoretically separated and electroblotted HIV antigens. The lectins concanavalin A, wheat germ agglutinin, Lens culinaris agglutinin, Vicia faba...... agglutinin, Pisum sativum agglutinin and phytohaem(erythro)agglutinin bound to gp120 of all three isolates. The carbohydrate of gp120 recognized by lectins was thus arranged in at least four types of glycans: a high mannose type glycan, a bisected hybrid or complex type glycan, a biantennary fucosylated...

  10. Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Bryan C. Au

    2016-02-01

    Full Text Available Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag-specific responses through direct injections of recombinant lentivectors (LVs that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months—the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an “off-the-shelf” anti-cancer vaccine that could be made at large scale and injected into patients—even on an out-patient basis.

  11. Treating cancer as an infectious disease--viral antigens as novel targets for treatment and potential prevention of tumors of viral etiology.

    Directory of Open Access Journals (Sweden)

    Xing Guo Wang

    Full Text Available BACKGROUND: Nearly 20% of human cancers worldwide have an infectious etiology with the most prominent examples being hepatitis B and C virus-associated hepatocellular carcinoma and human papilloma virus-associated cervical cancer. There is an urgent need to find new approaches to treatment and prevention of virus-associated cancers. METHODOLOGY/PRINCIPAL FINDINGS: Viral antigens have not been previously considered as targets for treatment or prevention of virus-associated cancers. We hypothesized that it was possible to treat experimental HPV16-associated cervical cancer (CC and Hepatitis B-associated hepatocellular carcinoma (HCC by targeting viral antigens expressed on cancer cells with radiolabeled antibodies to viral antigens. Treatment of experimental CC and HCC tumors with (188Re-labeled mAbs to E6 and HBx viral proteins, respectively, resulted in significant and dose-dependent retardation of tumor growth in comparison with untreated mice or mice treated with unlabeled antibodies. CONCLUSIONS/SIGNIFICANCE: This strategy is fundamentally different from the prior uses of radioimmunotherapy in oncology, which targeted tumor-associated human antigens and promises increased specificity and minimal toxicity of treatment. It also raises an exciting possibility to prevent virus-associated cancers in chronically infected patients by eliminating cells infected with oncogenic viruses before they transform into cancer.

  12. Food sources of carbohydrates in a European cohort of adults

    DEFF Research Database (Denmark)

    Wirfält, E.; McTaggart, A.; Pala, V.;

    2002-01-01

    participants only (men, women, after exclusion of subjects under 35 and over 74 years of age from the original 36 900 total). Dietary data were obtained using the 24-hour recall methodology using the EPIC-SOFT software. The major sources of dietary carbohydrate were identified, and 16 food groups were examined......OBJECTIVE: To describe the average consumption of carbohydrate-providing food groups among study centres of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: Of the 27 redefined EPIC study centres, 19 contributed subjects of both genders and eight centres female....... RESULTS: The 10 food groups contributing most carbohydrate were bread; fruit; milk and milk products; sweet buns, cakes and pies; potato; sugar and jam; pasta and rice; vegetables and legumes; crispbread; and fruit and vegetable juices. Consumption of fruits as well as vegetables and legumes was higher...

  13. Effects of polymeric carbohydrates on growth and development

    DEFF Research Database (Denmark)

    Knudsen, Knud Erik Bach

    ) and soluble NSP will influence the release of insulin, the hormone that facilitate nutrient uptake by tissues, organs and cells, and thus play a critical and essential role in protein synthesis and muscle growth as well as lipid synthesis and adipose tissue growth. In conclusion, polymeric carbohydrates......The main objective of the presentation is to provide insight into the role of polymeric carbohydrates in growth and development of pigs. Polymeric carbohydrates—starch and non-starch polysaccharides (NSP)—quantitatively represent the largest portion of the diets for pigs and are therefore...... at a slower and more constant rate and with SCFA being absorbed by passive diffusion. Type and levels of polymeric carbohydrates influence growth and development through different mechanisms; first, the proportion of starch to NSP plays an important role for the content of available energy (digestible...

  14. Effects of polymeric carbohydrates on growth and development in pigs

    DEFF Research Database (Denmark)

    Knudsen, Knud Erik Bach

    2011-01-01

    , organs, and cells, and thus plays a critically essential role in protein synthesis and muscle growth, as well as lipid synthesis and adipose tissue growth. In conclusion, polymeric carbohydrates influence growth and development through events in the gut and direct and indirect effects of different...... carbohydrates influence growth and development through different mechanisms. First, the proportion of starch to NSP plays an important role for the content of available energy (i.e., DE, ME, and NE); available energy relative to protein is crucial for performance and carcass quality. Second, the proportion...... of starch to NSP will influence rate and type of metabolites (i.e., glucose vs. SCFA) deriving from carbohydrate assimilation. Third and finally, the type of starch (i.e., types A, B, and C) and soluble NSP will influence the release of insulin, the hormone that facilitates nutrient uptake by tissues...

  15. Carbohydrate mimetics and scaffolds: sweet spots in medicinal chemistry.

    Science.gov (United States)

    Cipolla, Laura; La Ferla, Barbara; Airoldi, Cristina; Zona, Cristiano; Orsato, Alexandre; Shaikh, Nasrin; Russo, Laura; Nicotra, Francesco

    2010-04-01

    Several glycoprocessing enzymes and glycoreceptors have been recognized as important targets for therapeutic intervention. This concept has inspired the development of important classes of therapeutics, such as anti-influenza drugs inhibiting influenza virus neuraminidase, anti-inflammatory drugs targeting lectin-sialyl-Lewis X interaction and glycosidase inhibitors against HIV, Gaucher's disease, hepatitis and cancer. These therapeutics are mainly carbohydrate mimics in which proper modifications permit stronger interactions with the target protein, higher stability, better pharmacokinetic properties and easier synthesis. Furthermore, the conformational rigidity and polyfunctionality of carbohydrates stimulate their use as scaffolds for the generation of libraries by combinatorial decoration with different pharmacophores. This mini-review will present examples of how to exploit carbohydrates mimics and scaffolds in drug research. PMID:21426009

  16. Separation of carbohydrates using hydrophilic interaction liquid chromatography.

    Science.gov (United States)

    Fu, Qing; Liang, Tu; Li, Zhenyu; Xu, Xiaoyong; Ke, Yanxiong; Jin, Yu; Liang, Xinmiao

    2013-09-20

    A strategy was developed to rapidly evaluate chromatographic properties of hydrophilic interaction chromatography (HILIC) columns for separating carbohydrates. Seven HILIC columns (Silica, Diol, TSK Amide-80, XAmide, Click Maltose, Click β-CD, and Click TE-Cys columns) were evaluated by using three monosaccharide and seven disaccharides as probes. The influence of column temperature on the peak shape and tautomerization of carbohydrates, as well as column selectivity were investigated. The influence of surface charge property on the retention was also studied by using glucose, glucuronic acid, and glucosamine, which indicated that buffer salt concentration and pH value in mobile phase was necessary to control the ionic interactions between ionic carbohydrates and HILIC columns. According to evaluation results, the XAmide column was selected as an example to establish experimental schemes for separation of complex mixtures of oligosaccharide.

  17. Microalgal carbohydrates. An overview of the factors influencing carbohydrates production, and of main bioconversion technologies for production of biofuels

    Energy Technology Data Exchange (ETDEWEB)

    Markou, Giorgos; Georgakakis, Dimitris [Agricultural Univ. of Athens (Greece). Dept. of Natural Resources Management and Agricultural Engineering; Angelidaki, Irini [Technical Univ. of Denmark, Lyngby (Denmark). Dept. of Environmental Engineering

    2012-11-15

    Microalgal biomass seems to be a promising feedstock for biofuel generation. Microalgae have relative high photosynthetic efficiencies, high growth rates, and some species can thrive in brackish water or seawater and wastewater from the food- and agro-industrial sector. Today, the main interest in research is the cultivation of microalgae for lipids production to generate biodiesel. However, there are several other biological or thermochemical conversion technologies, in which microalgal biomass could be used as substrate. However, the high protein content or the low carbohydrate content of the majority of the microalgal species might be a constraint for their possible use in these technologies. Moreover, in the majority of biomass conversion technologies, carbohydrates are the main substrate for production of biofuels. Nevertheless, microalgae biomass composition could be manipulated by several cultivation techniques, such as nutrient starvation or other stressed environmental conditions, which cause the microalgae to accumulate carbohydrates. This paper attempts to give a general overview of techniques that can be used for increasing the microalgal biomass carbohydrate content. In addition, biomass conversion technologies, related to the conversion of carbohydrates into biofuels are discussed. (orig.)

  18. Antigen Incorporation on Cryptosporidium parvum Oocyst Walls

    OpenAIRE

    Entrala Emilio; Sbihi Younes; Sánchez-Moreno Manuel; Mascaró Carmen

    2001-01-01

    Cryptosporidium parvum oocysts are the infective stages responsible for transmission and survival of the organism in the environment. In the present work we show that the oocyst wall, far from being a static structure, is able to incorporate antigens by a mechanism involving vesicle fusion with the wall, and the incorporation of the antigen to the outer oocyst wall. Using immunoelectron microscopy we show that the antigen recognized by a monoclonal antibody used for diagnosis of cryptosporidi...

  19. Histocompatibility antigens in coal miners with pneumoconiosis.

    OpenAIRE

    Soutar, C A; Coutts, I.; Parkes, W R; Dodi, I. A.; Gauld, S; Castro, J E; Turner-Warwick, M

    1983-01-01

    Twenty-five histocompatibility antigens have been measured in 100 coal miners with pneumoconiosis attending a pneumoconiosis medical panel and the results compared with a panel of 200 normal volunteers not exposed to dust. Chest radiographs were read independently by three readers according to the ILO U/C classification. On a combined score, 40 men were thought to have simple pneumoconiosis and 60 men complicated pneumoconiosis. The number of antigens tested and associations between antigens ...

  20. Vina-Carb: Improving Glycosidic Angles during Carbohydrate Docking.

    Science.gov (United States)

    Nivedha, Anita K; Thieker, David F; Makeneni, Spandana; Hu, Huimin; Woods, Robert J

    2016-02-01

    Molecular docking programs are primarily designed to align rigid, drug-like fragments into the binding sites of macromolecules and frequently display poor performance when applied to flexible carbohydrate molecules. A critical source of flexibility within an oligosaccharide is the glycosidic linkages. Recently, Carbohydrate Intrinsic (CHI) energy functions were reported that attempt to quantify the glycosidic torsion angle preferences. In the present work, the CHI-energy functions have been incorporated into the AutoDock Vina (ADV) scoring function, subsequently termed Vina-Carb (VC). Two user-adjustable parameters have been introduced, namely, a CHI- energy weight term (chi_coeff) that affects the magnitude of the CHI-energy penalty and a CHI-cutoff term (chi_cutoff) that negates CHI-energy penalties below a specified value. A data set consisting of 101 protein-carbohydrate complexes and 29 apoprotein structures was used in the development and testing of VC, including antibodies, lectins, and carbohydrate binding modules. Accounting for the intramolecular energies of the glycosidic linkages in the oligosaccharides during docking led VC to produce acceptable structures within the top five ranked poses in 74% of the systems tested, compared to a success rate of 55% for ADV. An enzyme system was employed in order to illustrate the potential application of VC to proteins that may distort glycosidic linkages of carbohydrate ligands upon binding. VC represents a significant step toward accurately predicting the structures of protein-carbohydrate complexes. Furthermore, the described approach is conceptually applicable to any class of ligands that populate well-defined conformational states. PMID:26744922

  1. Characterization of carbohydrate-protein matrices for nutrient delivery.

    Science.gov (United States)

    Zhou, Yankun; Roos, Yrjö H

    2011-05-01

    Amorphous carbohydrates may show glass transition and crystallization as a result of thermal or water plasticization. Proteins often affect the state transitions of carbohydrates in carbohydrate-protein systems. Water sorption behavior and effects of water on glass transition and crystallization in freeze-dried lactose, trehalose, lactose-casein (3: 1), lactose-soy protein isolate (3:1), trehalose-casein (3:1), and trehalose-soy protein isolate (3:1) systems were studied. Water sorption was determined gravimetrically as a function of time, and Brunauer-Emmett-Teller (BET) and Guggenheim-Anderson-de Boer (GAB) models were fitted to the experimental data. Glass transition temperature (T(g)) and instant crystallization temperature (T(ic)) in anhydrous and water plasticized systems were measured using differential scanning calorimetry (DSC). The Gordon-Taylor equation was used to model water content dependence of the T(g) values. The critical water content and water activity (a(w)) at 24 °C were calculated and crystallization of lactose and trehalose in the systems was followed at and above 0.54 a(w). Carbohydrate-protein systems showed higher amounts of sorbed water and less rapid sugar crystallization than pure sugars. A greater sugar crystallization delay was found in carbohydrate-casein systems than in carbohydrate-soy protein isolate systems. The T(g) and T(ic) values decreased with increasing water content and a(w). However, higher T(ic) values for lactose-protein systems were found than for lactose at the same a(w). Trehalose showed lower T(ic) value than lactose at 0.44 a(w) but no instant crystallization was measured below 0.44 a(w). State diagrams for each system are useful in selecting processing parameters and storage conditions in nutrient delivery applications. PMID:22417357

  2. Diagnosing and Treating Intolerance to Carbohydrates in Children

    Directory of Open Access Journals (Sweden)

    Roberto Berni Canani

    2016-03-01

    Full Text Available Intolerance to carbohydrates is relatively common in childhood, but still poorly recognized and managed. Over recent years it has come to the forefront because of progresses in our knowledge on the mechanisms and treatment of these conditions. Children with intolerance to carbohydrates often present with unexplained signs and symptoms. Here, we examine the most up-to-date research on these intolerances, discuss controversies relating to the diagnostic approach, including the role of molecular analysis, and provide new insights into modern management in the pediatric age, including the most recent evidence for correct dietary treatment.

  3. Diagnosing and Treating Intolerance to Carbohydrates in Children.

    Science.gov (United States)

    Berni Canani, Roberto; Pezzella, Vincenza; Amoroso, Antonio; Cozzolino, Tommaso; Di Scala, Carmen; Passariello, Annalisa

    2016-03-01

    Intolerance to carbohydrates is relatively common in childhood, but still poorly recognized and managed. Over recent years it has come to the forefront because of progresses in our knowledge on the mechanisms and treatment of these conditions. Children with intolerance to carbohydrates often present with unexplained signs and symptoms. Here, we examine the most up-to-date research on these intolerances, discuss controversies relating to the diagnostic approach, including the role of molecular analysis, and provide new insights into modern management in the pediatric age, including the most recent evidence for correct dietary treatment.

  4. Diagnosing and Treating Intolerance to Carbohydrates in Children.

    Science.gov (United States)

    Berni Canani, Roberto; Pezzella, Vincenza; Amoroso, Antonio; Cozzolino, Tommaso; Di Scala, Carmen; Passariello, Annalisa

    2016-03-01

    Intolerance to carbohydrates is relatively common in childhood, but still poorly recognized and managed. Over recent years it has come to the forefront because of progresses in our knowledge on the mechanisms and treatment of these conditions. Children with intolerance to carbohydrates often present with unexplained signs and symptoms. Here, we examine the most up-to-date research on these intolerances, discuss controversies relating to the diagnostic approach, including the role of molecular analysis, and provide new insights into modern management in the pediatric age, including the most recent evidence for correct dietary treatment. PMID:26978392

  5. Methods for Shortening and Extending the Carbon Chain in Carbohydrates

    DEFF Research Database (Denmark)

    Monrad, Rune Nygaard

    2008-01-01

    Carbohydrates play a central role in a variety of physiological and pathological processes such as HIV, cancer and diabetes. The understanding of these processes and the development of specific therapeutic agents is relying on the ability to chemically synthesize unnatural sugars, glycoconjugates...... in this thesis focuses on the development and application of transition metal mediated methods for shortening and extending the carbon chain in carbohydrates thereby providing access to lower and higher sugars.A new catalytic procedure for shortening unprotected sugars by one carbon atom has been developed...

  6. Does caffeine alter muscle carbohydrate and fat metabolism during exercise?

    DEFF Research Database (Denmark)

    Graham, Terry E; Battram, Danielle S; Dela, Flemming;

    2008-01-01

    and carbohydrate metabolism. While caffeine certainly mobilizes fatty acids from adipose tissue, rarely have measures of the respiratory exchange ratio indicated an increase in fat oxidation. However, this is a difficult measure to perform accurately during exercise, and small changes could be physiologically...... important. The few studies examining human muscle metabolism directly have also supported the fact that there is no change in fat or carbohydrate metabolism, but these usually have had a small sample size. We combined the data from muscle biopsy analyses of several similar studies to generate a sample size...

  7. Importance of low carbohydrate diets in diabetes management

    Directory of Open Access Journals (Sweden)

    Hall RM

    2016-03-01

    Full Text Available Rosemary M Hall, Amber Parry Strong, Jeremy D KrebsCentre for Endocrine, Diabetes and Obesity Research, Capital and Coast District Health Board, Wellington, New Zealand Abstract: Dietary strategies are fundamental in the management of diabetes. Historically, strict dietary control with a low carbohydrate diet was the only treatment option. With increasingly effective medications, the importance of dietary change decreased. Recommendations focused on reducing dietary fat to prevent atherosclerotic disease, with decreasing emphasis on the amount and quality of carbohydrate. As the prevalence of obesity and diabetes escalates, attention has returned to the macronutrient composition of the diet. Very low carbohydrate diets (VLCD's have demonstrated effective initial weight loss and improvement in glycemic control, but difficult long-term acceptability and worsening lipid profile. Modifications to the very low carbohydrate (VLC have included limiting saturated fat and increasing carbohydrate (CHO and protein. Reducing saturated fat appears pivotal in reducing low-density lipoprotein (LDL cholesterol and may mitigate adverse effects of traditional VLCD's. Increased dietary protein enhances satiety, reduces energy intake, and improves glycemic homeostasis, but without sustained improvements in glycemic control or cardiovascular risk over and above the effect of weight loss. Additionally, recent studies in type 1 diabetes mellitus suggest promising benefits to diabetes control with low carbohydrate diets, without concerning effects on ketosis or hypoglycemia. Dietary patterns may highlight pertinent associations. For example, Mediterranean-style and paleolithic-type diets, low in fat and carbohydrate, are associated with reduced body weight and improved glycemic and cardiovascular outcomes in type 2 diabetes mellitus (T2DM. A feature of these dietary patterns is low refined CHO and sugar and higher fiber, and it is possible that increasing sugar

  8. Investigations of Reactive Carbohydrates in Glycosidic Bond Formation and Degradation

    DEFF Research Database (Denmark)

    Heuckendorff, Mads

    was to develop new synthetic methods to evolve the field of synthetic carbohydrate chemistry. In addition, easy methods for obtaining complex oligosaccharides are needed to accommodate biochemical research and drug development. Furthermore, the aim was to shed light on the complex mechanisms of glycosylation...... and hy rolysis of glycosides. This mechanistic insight can then be used to develop new synthetic methods and obtain a better understanding of already existing methods. In Chapter 1 general aspects of synthetic carbohydrate chemistry is described with an emphasis on elements that affects reactivity...

  9. KINETICS OF DELIGNIFICATION AND CARBOHYDRATE DEGRADATION DURING OXYGEN BLEACHING

    Institute of Scientific and Technical Information of China (English)

    K. L Nguyen

    2004-01-01

    Carbohydrate degradation during oxygen bleaching is associated with cleavage reactions. It is apparent that the loss of the cellulose DP (degree ofpolymisation)is strongly affected by the extent of the delignification. A strong linear correlation can be established between the DP of cellulose chains and the residual lignin in the pulp. The Nuclear Growth concept and Percolation Theory for heterogenous system can be combined to formulate kinetic models for both the delignification and the degradation of carbohydrate. The models prediction is statistically robust and can be applied to different pulps at different bleaching conditions.

  10. MicroRNAs对肿瘤相关巨噬细胞的趋化及表型的影响%Effects of microRNAs on the chemotaxis and polarization of tumor-associated macrophage

    Institute of Scientific and Technical Information of China (English)

    彭妍; 李国利; 张艳青

    2013-01-01

    The mononuclear macrophage is an important part of the innate immune response of the human body. Macrophages accumulate in tumor tissues, where they become tumor-associated macrophages. MiRNAs are small (22 nt) noncoding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region (3'-UTR) of specific messenger RNAs (mRNAs), resulting in mRNA degradation or translation repression. Many studies have found that miRNAs affect macrophage chemotaxis and dif-ferentiation through the regulation of chemokines and inflammatory cytokines. This review summarizes the advances in the research on the effects of microRNAs on the chemotaxis and polarization of tumor-associated macrophages.%  单核-巨噬细胞是机体固有免疫反应的重要组成部分,在肿瘤间质中浸润有大量巨噬细胞,被称为肿瘤相关巨噬细胞(tumor-associated macrophage,TAM).MicroRNAs(miRNAs,miRs)是一类由内源基因编码,长度约为22个核苷酸的非编码单链RNA 分子.miRNA与目标基因3'不翻译区(3'-UTR)结合,抑制靶蛋白的表达,在转录后水平对目标基因的表达水平进行调控.miRNAs可通过调控趋化因子及炎症因子影响巨噬细胞的趋化和分化.本文将近几年关于miRNAs对TAM的趋化及表型影响的研究结果进行综述.

  11. 极化型肿瘤相关巨噬细胞及其与卵巢癌的相关性%Development of Relativity between M2-Tumor Associated Macrophage and Ovarian Cancer

    Institute of Scientific and Technical Information of China (English)

    张洪秀; 陈燕

    2013-01-01

    肿瘤相关巨噬细胞(TAM)与肿瘤发生发展的关系一直以来都是肿瘤的病因及治疗的研究热点,实验及临床研究表明不同类型肿瘤的发生发展与TAM有密切关系.TAM是参与肿瘤相关性炎症的重要调节细胞,而在肿瘤微环境中表现促肿瘤生长的亚型主要为极化型(M2-TAM).M2-TAM通过趋化因子18(CCL-18)、血管内皮生长因子(VEGF)和基质金属蛋白酶9(MMP-9)等抑制T细胞的抗肿瘤活性并促进血管生成.因此,M2-TAM在肿瘤组织中的浸润情况可能是肿瘤发生、发展、转移及判断预后的一个重要指标,并为卵巢癌的治疗提供新的途径.综述M2-TAM在卵巢癌发生发展中的重要作用,并为卵巢癌的治疗及早期诊断提供新的方向.%Tumor-related inflammation including lymphocyte infiltration into tumor tissue. Tumor-associated macrophages (TAM) are important regulator of cells,mainly involved in tumor-associated inflammatory. While M2-tumor associated macrophage is the main subtype macrophages which expression in the tumor microenvironment, promote and coordinate neo-plastic growth. M2-type TAM inhibite the anti-tumor activity of T cells and promote angiogenesis by over expressing CCL-18, VEGF, and MMP-9. M2-type TAM infiltration in tumor tissue might be an important indicator of tumor development, metastasis and prognosis, and providing a new approach to treatment of ovarian cancer. Polarization-type tumor-associated macrophages play an important role in the development of ovarian cancer and provide a new direction in early diagnosis and treatment of ovarian cancer.

  12. Blood group antigen studies using CdTe quantum dots and flow cytometry

    Directory of Open Access Journals (Sweden)

    Cabral Filho PE

    2015-07-01

    , this methodology with high sensibility and specificity can be applied to study a variety of RBC antigens, and, as a quantitative tool, can help in achieving a better comprehension of the antigen expression patterns on RBC membranes. Keywords: erythrocytes, nanoparticles, ABO antigens, carbohydrates, covalent binding

  13. A computational framework for influenza antigenic cartography.

    Directory of Open Access Journals (Sweden)

    Zhipeng Cai

    Full Text Available Influenza viruses have been responsible for large losses of lives around the world and continue to present a great public health challenge. Antigenic characterization based on hemagglutination inhibition (HI assay is one of the routine procedures for influenza vaccine strain selection. However, HI assay is only a crude experiment reflecting the antigenic correlations among testing antigens (viruses and reference antisera (antibodies. Moreover, antigenic characterization is usually based on more than one HI dataset. The combination of multiple datasets results in an incomplete HI matrix with many unobserved entries. This paper proposes a new computational framework for constructing an influenza antigenic cartography from this incomplete matrix, which we refer to as Matrix Completion-Multidimensional Scaling (MC-MDS. In this approach, we first reconstruct the HI matrices with viruses and antibodies using low-rank matrix completion, and then generate the two-dimensional antigenic cartography using multidimensional scaling. Moreover, for influenza HI tables with herd immunity effect (such as those from Human influenza viruses, we propose a temporal model to reduce the inherent temporal bias of HI tables caused by herd immunity. By applying our method in HI datasets containing H3N2 influenza A viruses isolated from 1968 to 2003, we identified eleven clusters of antigenic variants, representing all major antigenic drift events in these 36 years. Our results showed that both the completed HI matrix and the antigenic cartography obtained via MC-MDS are useful in identifying influenza antigenic variants and thus can be used to facilitate influenza vaccine strain selection. The webserver is available at http://sysbio.cvm.msstate.edu/AntigenMap.

  14. A computational framework for influenza antigenic cartography.

    Science.gov (United States)

    Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

    2010-10-07

    Influenza viruses have been responsible for large losses of lives around the world and continue to present a great public health challenge. Antigenic characterization based on hemagglutination inhibition (HI) assay is one of the routine procedures for influenza vaccine strain selection. However, HI assay is only a crude experiment reflecting the antigenic correlations among testing antigens (viruses) and reference antisera (antibodies). Moreover, antigenic characterization is usually based on more than one HI dataset. The combination of multiple datasets results in an incomplete HI matrix with many unobserved entries. This paper proposes a new computational framework for constructing an influenza antigenic cartography from this incomplete matrix, which we refer to as Matrix Completion-Multidimensional Scaling (MC-MDS). In this approach, we first reconstruct the HI matrices with viruses and antibodies using low-rank matrix completion, and then generate the two-dimensional antigenic cartography using multidimensional scaling. Moreover, for influenza HI tables with herd immunity effect (such as those from Human influenza viruses), we propose a temporal model to reduce the inherent temporal bias of HI tables caused by herd immunity. By applying our method in HI datasets containing H3N2 influenza A viruses isolated from 1968 to 2003, we identified eleven clusters of antigenic variants, representing all major antigenic drift events in these 36 years. Our results showed that both the completed HI matrix and the antigenic cartography obtained via MC-MDS are useful in identifying influenza antigenic variants and thus can be used to facilitate influenza vaccine strain selection. The webserver is available at http://sysbio.cvm.msstate.edu/AntigenMap.

  15. The factors affecting on estimation of carbohydrate content of meals in carbohydrate counting.

    Science.gov (United States)

    Kawamura, Tomoyuki; Takamura, Chihiro; Hirose, Masakazu; Hashimoto, Tomomi; Higashide, Takashi; Kashihara, Yoneo; Hashimura, Kayako; Shintaku, Haruo

    2015-10-01

    The objective of this study was to identify factors affecting on errors in carbohydrate (CHO) content estimation during CHO counting. Thirty-seven type 1 diabetes patients and 22 of their parents and 28 physicians/dieticians were enrolled in this study. CHO counting was counted in "Carb", with 1 Carb defined as 10 g of CHO. To evaluate the accuracy of CHO counting, 80 real-size photographs of cooked meals were presented to the subjects for Carb estimation. Carbs tended to be overestimated for foods containing relatively small amounts of Carbs. On the other hands, Carbs tended to be underestimated for foods with higher than 6 Carbs. Accurate estimation of the Carbs in food containing a large amount of rice was particularly difficult even in the subjects having the CHO counting experience. The Carb contents of high-calorie foods such as meats, fried foods, and desserts tended to be overestimated. This error was smaller in subjects having the CHO counting experience. In conclusion, misunderstanding of high-calorie dishes containing high amounts of CHO was observed in inexperienced subjects, indicating the efficacy of the current methodology of CHO counting. On the other hand it was difficult even for experienced subjects to assess the amount of seasoned rice, suggesting the need for a new methodology for accurate estimation. PMID:26568656

  16. Electro-optical study of the exposure of Azospirillum brasilense carbohydrate epitopes.

    Science.gov (United States)

    Guliy, Olga I; Matora, Larisa Yu; Dykman, Lev A; Staroverov, Sergey A; Burygin, Gennady L; Bunin, Viktor D; Burov, Andrei M; Ignatov, Oleg V

    2015-01-01

    The exposure of Azospirillum brasilense carbohydrate epitopes was investigated by electro-optical analysis of bacterial cell suspensions. To study changes in the electro-optical (EO) properties of the suspensions, we used antibodies generated to the complete lipopolysaccharide of A. brasilense type strain Sp7 and also antibodies to the smooth and rough O polysaccharides of Sp7. After 18 hr of culture growth, the EO signal of the suspension treated with antibodies to smooth O polysaccharide was approximately 20% lower than that of the suspension treated with antibodies to complete lipopolysaccharide (control). After 72 hr of culture growth, the strongest EO signal was observed for the cells treated with antibodies to rough O polysaccharide (approximately 46% greater than the control), whereas for the cells treated with antibodies to smooth O polysaccharide, it was much lower (approximately 23% of the control). These data were confirmed by electron microscopy. The results of the study may have importance for the rapid evaluation of changes in lipopolysaccharide form in microbial biotechnology, when the antigenic composition of the bacterial surface requires close control.

  17. Effects of CO₂ on Acer negundo pollen fertility, protein content, allergenic properties, and carbohydrates.

    Science.gov (United States)

    Silva, M; Ribeiro, H; Abreu, I; Cruz, A; Esteves da Silva, J C G

    2015-05-01

    Atmospheric gaseous pollutants can induce qualitative and quantitative changes in airborne pollen characteristics. In this work, it was investigated the effects of carbon dioxide (CO2) on Acer negundo pollen fertility, protein content, allergenic properties, and carbohydrates. Pollen was collected directly from the anthers and in vitro exposed to three CO2 levels (500, 1000, and 3000 ppm) for 6 and 24 h in an environmental chamber. Pollen fertility was determined using viability and germination assays, total soluble protein was determined with Coomassie Protein Assay Reagent, and the antigenic and allergenic properties were investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and immunological techniques using patients' sera. Also, pollen fructose, sucrose, and glucose values were determined. Carbon dioxide exposure affected negatively pollen fertility, total soluble protein content, and fructose content. The patient sera revealed increased IgE reactivity to proteins of A. negundo pollen exposed to increasing levels of the pollutant. No changes were detected in the SDS-PAGE protein profiles and in sucrose and glucose levels. Our results indicate that increase in atmospheric CO2 concentrations can have a negative influence of some features of A. negundo airborne pollen that can influence the reproductive processes as well as respiratory pollen allergies in the future.

  18. Terrestrial carbohydrates support freshwater zooplankton during phytoplankton deficiency.

    Science.gov (United States)

    Taipale, Sami J; Galloway, Aaron W E; Aalto, Sanni L; Kahilainen, Kimmo K; Strandberg, Ursula; Kankaala, Paula

    2016-01-01

    Freshwater food webs can be partly supported by terrestrial primary production, often deriving from plant litter of surrounding catchment vegetation. Although consisting mainly of poorly bioavailable lignin, with low protein and lipid content, the carbohydrates from fallen tree leaves and shoreline vegetation may be utilized by aquatic consumers. Here we show that during phytoplankton deficiency, zooplankton (Daphnia magna) can benefit from terrestrial particulate organic matter by using terrestrial-origin carbohydrates for energy and sparing essential fatty acids and amino acids for somatic growth and reproduction. Assimilated terrestrial-origin fatty acids from shoreline reed particles exceeded available diet, indicating that Daphnia may convert a part of their dietary carbohydrates to saturated fatty acids. This conversion was not observed with birch leaf diets, which had lower carbohydrate content. Subsequent analysis of 21 boreal and subarctic lakes showed that diet of herbivorous zooplankton is mainly based on high-quality phytoplankton rich in essential polyunsaturated fatty acids. The proportion of low-quality diets (bacteria and terrestrial particulate organic matter) was zooplankton was not directly related to the concentration of terrestrial organic matter in experiments or lakes, but rather to the low availability of phytoplankton. PMID:27510848

  19. Protective group strategies in carbohydrate and peptide chemistry

    NARCIS (Netherlands)

    Ali, Asghar

    2010-01-01

    Protecting groups play a key role in the synthesis of complex natural products.This holds especially true for the synthesis of oligosaccharides, of which the monomeric carbohydrate building blocks usually contain up to five different hydroxyl functions. The discrimination of these hydroxyl functions

  20. Sulfurised carbohydrates: An important sedimentary sink for organic carbon?

    NARCIS (Netherlands)

    Sinninghe Damsté, J.S.; Kok, M.D.; Koster, J.; Schouten, S.

    1998-01-01

    In contrast to the general belief that carbohydrate carbon (CCHO) is preferentially degraded and is not extensively preserved in the sedimentary record, it is shown here that CCHO forms a large fraction of the organic matter (OM) of the total organic carbon (TOC)-rich upper Jurassic Kimmeridge Clay

  1. Martini Coarse-Grained Force Field : Extension to Carbohydrates

    NARCIS (Netherlands)

    Lopez, Cesar A.; Rzepiela, Andrzej J.; de Vries, Alex H.; Dijkhuizen, Lubbert; Huenenberger, Philippe H.; Marrink, Siewert J.; Hünenberger, Philippe H.

    2009-01-01

    We present an extension of the Martini coarse-grained force field to carbohydrates. The parametrization follows the same philosophy as was used previously for lipids and proteins, focusing on the reproduction of partitioning free energies of small compounds between polar and nonpolar phases. The car

  2. Terrestrial carbohydrates support freshwater zooplankton during phytoplankton deficiency

    Science.gov (United States)

    Taipale, Sami J.; Galloway, Aaron W. E.; Aalto, Sanni L.; Kahilainen, Kimmo K.; Strandberg, Ursula; Kankaala, Paula

    2016-01-01

    Freshwater food webs can be partly supported by terrestrial primary production, often deriving from plant litter of surrounding catchment vegetation. Although consisting mainly of poorly bioavailable lignin, with low protein and lipid content, the carbohydrates from fallen tree leaves and shoreline vegetation may be utilized by aquatic consumers. Here we show that during phytoplankton deficiency, zooplankton (Daphnia magna) can benefit from terrestrial particulate organic matter by using terrestrial-origin carbohydrates for energy and sparing essential fatty acids and amino acids for somatic growth and reproduction. Assimilated terrestrial-origin fatty acids from shoreline reed particles exceeded available diet, indicating that Daphnia may convert a part of their dietary carbohydrates to saturated fatty acids. This conversion was not observed with birch leaf diets, which had lower carbohydrate content. Subsequent analysis of 21 boreal and subarctic lakes showed that diet of herbivorous zooplankton is mainly based on high-quality phytoplankton rich in essential polyunsaturated fatty acids. The proportion of low-quality diets (bacteria and terrestrial particulate organic matter) was directly related to the concentration of terrestrial organic matter in experiments or lakes, but rather to the low availability of phytoplankton. PMID:27510848

  3. Architectures of Multivalent Glycomimetics for Probing Carbohydrate-Lectin Interactions

    Science.gov (United States)

    Lahmann, Martina

    Well-defined multivalent glycoconjugates are valued tools in glycoscience and they are particularly valuable for the investigation of carbohydrate-lectin interactions. In addition to the relatively globularly shaped glycodendrimers many other designs have been realized. This chapter gives an overview on the common different architectures and their chemical synthesis by focussing on the achievements made since 2001.

  4. Radiation degradation of carbohydrates and their biological activities for plants

    Energy Technology Data Exchange (ETDEWEB)

    Kume, T.; Nagasawa, N.; Matsuhashi, S. [Japan Atomic Energy Research Inst., Takasaki, Gunma (Japan). Takasaki Radiation Chemistry Research Establishment] [and others

    2000-03-01

    Radiation effects on carbohydrates such as chitosan, sodium alginate, carrageenan, cellulose, pectin have been investigated to improve the biological activities. These carbohydrates were easily degraded by irradiation and induced various kinds of biological activities such as anti-bacterial activity, promotion of plant growth, suppression of heavy metal stress, phytoalexins induction. Pectic fragments obtained from degraded pectin induced the phytoalexins such as glyceollins in soybean and pisatin in pea. The irradiated chitosan shows the higher elicitor activity for pisatin than that of pectin. For the plant growth promotion, alginate derived from brown marine algae, chitosan and ligno-cellulosic extracts show a strong activity. Kappa and iota carrageenan derived from red marine algae can promote growth of rice and the highest effect was obtained with kappa irradiated at 100 kGy. Some radiation degraded carbohydrates suppressed the damage of heavy metals on plants. The effects of irradiated carbohydrates on transportation of heavy metals have been investigated by PETIS (Positron Emitting Tracer Imaging System) and autoradiography using {sup 48}V and {sup 62}Zn. (author)

  5. Radiation degradation of carbohydrates and their biological activities for plants

    International Nuclear Information System (INIS)

    Radiation effects on carbohydrates such as chitosan, sodium alginate, carrageenan, cellulose, pectin have been investigated to improve the biological activities. These carbohydrates were easily degraded by irradiation and induced various kinds of biological activities such as anti-bacterial activity, promotion of plant growth, suppression of heavy metal stress, phytoalexins induction. Pectic fragments obtained from degraded pectin induced the phytoalexins such as glyceollins in soybean and pisatin in pea. The irradiated chitosan shows the higher elicitor activity for pisatin than that of pectin. For the plant growth promotion, alginate derived from brown marine algae, chitosan and ligno-cellulosic extracts show a strong activity. Kappa and iota carrageenan derived from red marine algae can promote growth of rice and the highest effect was obtained with kappa irradiated at 100 kGy. Some radiation degraded carbohydrates suppressed the damage of heavy metals on plants. The effects of irradiated carbohydrates on transportation of heavy metals have been investigated by PETIS (Positron Emitting Tracer Imaging System) and autoradiography using 48V and 62Zn. (author)

  6. Advancing Analytical Methods for Characterization of Anionic Carbohydrate Biopolymers

    OpenAIRE

    Langeslay, Derek Joseph

    2013-01-01

    The focus of this dissertation is on the development of improved analytical methods for the characterization of anionic carbohydrate biopolymers. Our goal is to extract important information from complex mixtures of heterogeneous polysaccharides by characterizing their substituent oligosaccharides in terms of monosaccharide composition and primary and secondary structure. This work focuses on the application of two major analytical platforms: spectroscopy and chromatography. The development ...

  7. Horizontal transfer of carbohydrate metabolism genes into ectomycorrhizal Amanita

    NARCIS (Netherlands)

    Chaib De Mares, Maryam; Hess, Jaqueline; Floudas, Dimitrios; Lipzen, Anna; Choi, Cindy; Kennedy, Megan; Grigoriev, Igor V.; Pringle, Anne

    2015-01-01

    - The genus Amanita encompasses both symbiotic, ectomycorrhizal fungi and asymbiotic litter decomposers; all species are derived from asymbiotic ancestors. Symbiotic species are no longer able to degrade plant cell walls. The carbohydrate esterases family 1 (CE1s) is a diverse group of enzymes invol

  8. Linking Bacillus cereus genotypes and carbohydrate utilization capacity

    NARCIS (Netherlands)

    Warda, Alicja K.; Siezen, Roland J.; Boekhorst, Jos; Wells-Bennik, Marjon H.J.; Jong, de Anne; Kuipers, Oscar P.; Nierop Groot, Masja N.; Abee, Tjakko

    2016-01-01

    We characterised carbohydrate utilisation of 20 newly sequenced Bacillus cereus strains isolated from food products and food processing environments and two laboratory strains, B. cereus ATCC 10987 and B. cereus ATCC 14579. Subsequently, genome sequences of these strains were analysed together wi

  9. Linking Bacillus cereus Genotypes and Carbohydrate Utilization Capacity

    NARCIS (Netherlands)

    Warda, Alicja K.; Siezen, Roland J.; Boekhorst, Jos; Wells-Bennik, Marjon H.J.; Jong, de Anne; Kuipers, Oscar P.; Nierop Groot, Masja N.; Abee, Tjakko

    2016-01-01

    We characterised carbohydrate utilisation of 20 newly sequenced Bacillus cereus strains isolated from food products and food processing environments and two laboratory strains, B. cereus ATCC 10987 and B. cereus ATCC 14579. Subsequently, genome sequences of these strains were analysed together with

  10. Science Study Aids 3: Carbohydrates - Nature's Energy Source.

    Science.gov (United States)

    McConnell, Bill

    This publication is the third of a series of seven supplementary investigative materials for use in secondary science classes providing up-to-date research-related investigations. This unit is structured for grade levels 7 through 12. It is concerned with the role of carbohydrates as important nutrients for consumers. This guide will enable…

  11. Syntheses of Novel Highly Symmetric Carbohydrates Bearing Diacylhydrazine Framework

    Institute of Scientific and Technical Information of China (English)

    YANG Bo; ZHANG Shu-sheng; LI Hui-xiang; LI Ji-zhi; JIAO Kui

    2005-01-01

    Several novel highly symmetric carbohydrates bearing a diacylhydrazine framework have been synthesized via a five-step procedure by utilizing D-glucose, D-galactose and D-xylose as the starting materials, respectively. The target compounds have been characterized with IR, 1H NMR and elemental analysis.

  12. Effects of specific carbohydrates on the intestinal microbiota

    DEFF Research Database (Denmark)

    Hemmingsen, Lene; Holck, Jesper; Meyer, Anne S.;

    The current screening study aimed at testing a set of well-characterized carbohydrates derived from pectic oligosaccharides (POS) from sugar beet for their specific effect on intestinal microbiotas derived from healthy people and from patients suffering from the inflammatory bowel disease...

  13. Virosomes for antigen and DNA delivery

    NARCIS (Netherlands)

    Daemen, T; de Mare, A; Bungener, L; de Jonge, J; Huckriede, A; Wilschut, J

    2005-01-01

    Specific targeting and delivery as well as the display of antigens on the surface of professional antigen-presenting cells (APCs) are key issues in the design and development of new-generation vaccines aimed at the induction of both humoral and cell-mediated immunity. Prophylactic vaccination agains

  14. Differences in carbohydrate profiles in batch culture grown planktonic and biofilm cells of Amphora rostrata Wm. Sm

    Digital Repository Service at National Institute of Oceanography (India)

    Khodse, V.B.; Bhosle, N.B.

    modes of growth, the concentration of total carbohydrates, carbohydrate fractions, neutral carbohydrates, uronic acids and amino sugars in planktonic and biofilm cells of Amphora rostrata were measured. The results showed that the distribution...

  15. Protein antigen delivery by gene gun-mediated epidermal antigen incorporation (EAI).

    Science.gov (United States)

    Scheiblhofer, Sandra; Ritter, Uwe; Thalhamer, Josef; Weiss, Richard

    2013-01-01

    The gene gun technology can not only be employed for efficient transfer of gene vaccines into upper layers of the skin, but also for application of protein antigens. As a tissue rich in professional antigen presenting cells, the skin represents an attractive target for immunizations. In this chapter we present a method for delivery of the model antigen ovalbumin into the skin of mice termed epidermal antigen incorporation and describe in detail how antigen-specific proliferation in draining lymph nodes can be followed by flow cytometry.

  16. Functions of tumor-testis antigen and its application for tumor immunotherapy%肿瘤-睾丸抗原的功能与肿瘤免疫治疗

    Institute of Scientific and Technical Information of China (English)

    林丽燕

    2010-01-01

    肿瘤-睾丸抗原(CTA)是一类肿瘤相关性抗原,在多种肿瘤组织中表达,仅在少数正常组织表达.CTA功能众多,至今仍未完全明了,该抗原具有致免疫原性,在体内可产生细胞和体液免疫应答,为肿瘤免疫治疗提供了新的途径.%Cancer-testis antigen (CTA) is a kind of tumor-associated antigen, which expresses in various types of human tumor tissues but only express in a few of normal tissues. The CTA has numerous functions that not yet are fully understood. The CTA possesses immunogenicity that may induce cellular and humoral responses in vivo, which can provide a new approach for cancer immunotherapy.

  17. Water and carbohydrate content at leafs of plants used in medicine during vegetation

    Directory of Open Access Journals (Sweden)

    Zhivetev M.A.

    2011-12-01

    Full Text Available Increase of carbohydrate content with cryoprotective function to the end of vegetation period was shown. The accumulation of carbohydrates in plants on Lake Baikal shores region was greater than it in Irkutsk region.

  18. Dietary carbohydrate composition can change waste production and biofilter load in recirculating aquaculture systems

    NARCIS (Netherlands)

    Meriac, A.; Eding, E.H.; Schrama, J.W.; Kamstra, A.; Verreth, J.A.J.

    2014-01-01

    This study investigated the effect of dietary carbohydrate composition on the production, recovery and degradability of fecal waste from rainbow trout (Oncorhynchus mykiss) in recirculating aquaculture systems (RAS). Dietary carbohydrate composition was altered by substituting starch with non-starch

  19. Dietary advices on carbohydrate intake for pregnant women with type 1 diabetes

    DEFF Research Database (Denmark)

    Roskjær, Ann B; Andersen, Jens Rikardt; Ronneby, Helle;

    2015-01-01

    of Medicine (IOM) is generally recommended. A low-glycaemic index diet is considered safe, and has shown, positive effects on the glycaemic control and pregnancy outcomes for both healthy women, those with type 2 diabetic and gestational diabetes (GDM). In general, carbohydrate counting does improve glycaemic...... control in type 1 diabetes. A moderately low carbohydrate diet with a carbohydrate content of 40% of the calories results in better glycaemic control and comparable obstetric outcomes in type 2 diabetes and GDM when compared to a diet with a higher carbohydrate content, and is regarded safe in diabetic...... pregnancy. In type 1 diabetes pregnancy, a moderately low carbohydrate diet with 40% carbohydrates has been suggested; however, a minimum intake of 175 g carbohydrate daily is recommended. Despite limited evidence the combination of a low-glycaemic index diet with a moderately low carbohydrate intake, using...

  20. [Systematic evaluation of retention behavior of carbohydrates in hydrophilic interaction liquid chromatography].

    Science.gov (United States)

    Fu, Qing; Wang, Jun; Liang, Tu; Xu, Xiaoyong; Jin, Yu

    2013-11-01

    A systematic evaluation of retention behavior of carbohydrates in hydrophilic interaction liquid chromatography (HILIC) was performed. The influences of mobile phase, stationary phase and buffer salt on the retention of carbohydrates were investigated. According to the results, the retention time of carbohydrates decreased as the proportion of acetonitrile in mobile phase decreased. Increased time of carbohydrates was observed as the concentration of buffer salt in mobile phase increased. The retention behavior of carbohydrates was also affected by organic solvent and HILIC stationary phase. Furthermore, an appropriate retention equation was used in HILIC mode. The retention equation lnk = a + blnC(B) + cC(B) could quantitatively describe the retention factors of carbohydrates of plant origin with good accuracy: the relative error of the predicted time to actual time was less than 0.3%. The evaluation results could provide guidance for carbohydrates to optimize the experimental conditions in HILIC method development especially for carbohydrate separation