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Sample records for glycosylated cancer related

  1. Hallmarks of glycosylation in cancer.

    Science.gov (United States)

    Munkley, Jennifer; Elliott, David J

    2016-06-07

    Aberrant glycosylation plays a fundamental role in key pathological steps of tumour development and progression. Glycans have roles in cancer cell signalling, tumour cell dissociation and invasion, cell-matrix interactions, angiogenesis, metastasis and immune modulation. Aberrant glycosylation is often cited as a 'hallmark of cancer' but is notably absent from both the original hallmarks of cancer and from the next generation of emerging hallmarks. This review discusses how glycosylation is clearly an enabling characteristic that is causally associated with the acquisition of all the hallmark capabilities. Rather than aberrant glycosylation being itself a hallmark of cancer, another perspective is that glycans play a role in every recognised cancer hallmark.

  2. Glycosylation: a hallmark of cancer?

    Science.gov (United States)

    Vajaria, Bhairavi N; Patel, Prabhudas S

    2017-04-01

    The hallmarks of cancer are characterized by functional capabilities that allow cancer cells to survive, proliferate and disseminate during the multistep tumorigenesis. Cancer being a cellular disease, changes in cellular glycoproteins play an important role in malignant transformation and cancer progression. The present review summarizes various studies that depicted correlation of glycosylation with tumor initiation, progression and metastasis, which are helpful in early diagnosis, disease monitoring and prognosis. The results are further strengthened by our reports, which depicted alterations in sialylation and fucosylation in different cancers. Alterations in glycosyltransferases are also involved in formation of various tumor antigens (e.g. Sialyl Lewis x) which serves as ligand for the cell adhesion molecule, selectin which is involved in adhesion of cancer cells to vascular endothelium and thus contributes to hematogenous metastasis. Increased glycosylation accompanied by alterations in glycosyltranferases, glycosidases, glycans and mucins (MUC)s are also involved in loss of E-cadherin, a key molecule implicated in metastatic dissemination of cells. The present review also summarizes the correlation of glycosylation with all the hallmarks of cancer. The enormous progress in the design of novel inhibitors of pathway intermediates of sialylation and fucosylation can prove wonders in combating the dreadful disease. The results provide the evidence that altered glycosylation is linked to tumor initiation, progression and metastasis. Hence, it can be considered as a new hallmark of cancer development and strategies to develop novel glycosylation targeted molecules should be strengthened.

  3. Involvement of Aberrant Glycosylation in Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Eiji Miyoshi

    2010-01-01

    Full Text Available Glycosylation is one of the most common posttranslational modification reactions and nearly half of all known proteins in eukaryotes are glycosylated. In fact, changes in oligosaccharides structures are associated with many physiological and pathological events, including cell growth, migration and differentiation, and tumor invasion. Therefore, functional glycomics, which is a comprehensive study of the structures and functions of glycans, is attracting the increasing attention of scientists in various fields of life science. In cases of thyroid cancer, the biological characters and prognosis are completely different in each type of histopathology, and their oligosaccharide structures as well as the expression of glycosyltransferases are also different. In this review, we summarized our previous papers on oligosaccharides and thyroid cancers and discussed a possible function of oligosaccharides in the carcinogenesis in thyroid cancer.

  4. Glycosylation status of vitamin D binding protein in cancer patients.

    Science.gov (United States)

    Rehder, Douglas S; Nelson, Randall W; Borges, Chad R

    2009-10-01

    On the basis of the results of activity studies, previous reports have suggested that vitamin D binding protein (DBP) is significantly or even completely deglycosylated in cancer patients, eliminating the molecular precursor of the immunologically important Gc macrophage activating factor (GcMAF), a glycosidase-derived product of DBP. The purpose of this investigation was to directly determine the relative degree of O-linked trisaccharide glycosylation of serum-derived DBP in human breast, colorectal, pancreatic, and prostate cancer patients. Results obtained by electrospray ionization-based mass spectrometric immunoassay showed that there was no significant depletion of DBP trisaccharide glycosylation in the 56 cancer patients examined relative to healthy controls. These results suggest that alternative hypotheses regarding the molecular and/or structural origins of GcMAF must be considered to explain the relative inability of cancer patient serum to activate macrophages.

  5. Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics.

    Science.gov (United States)

    Kirwan, Alan; Utratna, Marta; O'Dwyer, Michael E; Joshi, Lokesh; Kilcoyne, Michelle

    2015-01-01

    Cancer is the second most common cause of death in developed countries with approximately 14 million newly diagnosed individuals and over 6 million cancer-related deaths in 2012. Many cancers are discovered at a more advanced stage but better survival rates are correlated with earlier detection. Current clinically approved cancer biomarkers are most effective when applied to patients with widespread cancer. Single biomarkers with satisfactory sensitivity and specificity have not been identified for the most common cancers and some biomarkers are ineffective for the detection of early stage cancers. Thus, novel biomarkers with better diagnostic and prognostic performance are required. Aberrant protein glycosylation is well known hallmark of cancer and represents a promising source of potential biomarkers. Glycoproteins enter circulation from tissues or blood cells through active secretion or leakage and patient serum is an attractive option as a source for biomarkers from a clinical and diagnostic perspective. A plethora of technical approaches have been developed to address the challenges of glycosylation structure detection and determination. This review summarises currently utilised glycoprotein biomarkers and novel glycosylation-based biomarkers from the serum glycoproteome under investigation as cancer diagnostics and for monitoring and prognostics and includes details of recent high throughput and other emerging glycoanalytical techniques.

  6. N-glycosylation of Colorectal Cancer Tissues

    Science.gov (United States)

    Balog, Crina I. A.; Stavenhagen, Kathrin; Fung, Wesley L. J.; Koeleman, Carolien A.; McDonnell, Liam A.; Verhoeven, Aswin; Mesker, Wilma E.; Tollenaar, Rob A. E. M.; Deelder, André M.; Wuhrer, Manfred

    2012-01-01

    Colorectal cancer is the third most common cancer worldwide with an annual incidence of ∼1 million cases and an annual mortality rate of ∼655,000 individuals. There is an urgent need for identifying novel targets to develop more sensitive, reliable, and specific tests for early stage detection of colon cancer. Post-translational modifications are known to play an important role in cancer progression and immune surveillance of tumors. In the present study, we compared the N-glycan profiles from 13 colorectal cancer tumor tissues and corresponding control colon tissues. The N-glycans were enzymatically released, purified, and labeled with 2-aminobenzoic acid. Aliquots were profiled by hydrophilic interaction liquid chromatography (HILIC-HPLC) with fluorescence detection and by negative mode MALDI-TOF-MS. Using partial least squares discriminant analysis to investigate the N-glycosylation changes in colorectal cancer, an excellent separation and prediction ability were observed for both HILIC-HPLC and MALDI-TOF-MS data. For structure elucidation, information from positive mode ESI-ion trap-MS/MS and negative mode MALDI-TOF/TOF-MS was combined. Among the features with a high separation power, structures containing a bisecting GlcNAc were found to be decreased in the tumor, whereas sulfated glycans, paucimannosidic glycans, and glycans containing a sialylated Lewis type epitope were shown to be increased in tumor tissues. In addition, core-fucosylated high mannose N-glycans were detected in tumor samples. In conclusion, the combination of HILIC and MALDI-TOF-MS profiling of N-glycans with multivariate statistical analysis demonstrated its potential for identifying N-glycosylation changes in colorectal cancer tissues and provided new leads that might be used as candidate biomarkers. PMID:22573871

  7. The role of glycosylation in breast cancer metastasis and cancer control

    Directory of Open Access Journals (Sweden)

    Alexandra eKölbl

    2015-10-01

    Full Text Available AbstractGlycosylation and its correlation to the formation of remote metastasis in breast cancer had been an important scientific topic in the last 25 years. With the development of new analytical techniques new insights were gained on the mechanisms underlying metastasis formation and the role of aberrant glycosylation within. Mucin-1 and Galectin were recognized as key players in glycosylation. Interestingly, aberrant carbohydrate structures seem to support the development of brain metastasis in breast cancer patients, as changes in glycosylation structures facilitate an overcoming of blood-brain barrier. Changes in the gene expression of glycosyltransferases are the leading cause for a modification of carbohydrate chains, so that also altered gene expression plays a role for glycosylation. In consequence, glycosylation and changes within can be useful for cancer diagnosis, determination of tumour stage and prognosis, but can as well be targets for therapeutic strategies. Thus, further research on this topic would worth wile for cancer combating.

  8. ECM Proteins Glycosylation and Relation to Diabetes

    Science.gov (United States)

    Pernodet, Nadine; Bloomberg, Ayla; Sood, Vandana; Slutsky, Lenny; Ge, Shouren; Clark, Richard; Rafailovich, Miriam

    2004-03-01

    The chemical modification and crosslinking of proteins by sugar glycosylation contribute to the aging of tissue proteins, and acceleration of this reaction during hyperglycemia is implicated in the pathogenesis of diabetic complications, such as disorder of the wound healing. Advanced glycation endproducts (AGEs) formation and protein crosslinking are irreversible processes that alter the structural and functional properties of proteins, lipid components and nucleic acids. And the mechanism, by which it happens, is not clear. Fibrinogen and fibronectin are plasma proteins, which play a major role in human wound healing. Fibrinogen converts to an insoluble fibrin "gel" following a cut, which eventually forms a clot to prevent blood loss, to direct cell adhesion and migration for forming scars. Fibronectin is a critical protein for cell adhesion and migration in wound healing. The effects of glucose on the binding of these plasma proteins from the extra cellular matrix (ECM) were followed at different concentrations by atomic force microscopy and lateral force modulation to measure the mechanical response of the samples. Glucose solutions (1, 2, and 3mg/mL) were incubated with the protein (100 mg/ml) and silicon (Si) substrates spun with sulfonated polystyrene (SPS) 28% for five days. Data showed that not only the organization of the protein on the surface was affected but also its mechanical properties. At 3 mg/mL glucose, Fn fibers were observed to be harder than those of the control, in good agreement with our hypothesis that glycosylation hardens tissues by crosslinking of proteins in the ECM and might cause fibers to break more easily.

  9. Cancer associated aberrant protein o-glycosylation can modify antigen processing and immune response

    DEFF Research Database (Denmark)

    Madsen, Caroline B; Petersen, Cecilie; Lavrsen, Kirstine

    2012-01-01

    Aberrant glycosylation of mucins and other extracellular proteins is an important event in carcinogenesis and the resulting cancer associated glycans have been suggested as targets in cancer immunotherapy. We assessed the role of O-linked GalNAc glycosylation on antigen uptake, processing......, and presentation on MHC class I and II molecules. The effect of GalNAc O-glycosylation was monitored with a model system based on ovalbumin (OVA)-MUC1 fusion peptides (+/- glycosylation) loaded onto dendritic cells co-cultured with IL-2 secreting OVA peptide-specific T cell hybridomas. To evaluate the in vivo...

  10. Characterization of kallikrein-related peptidase 4 glycosylations.

    Science.gov (United States)

    Yamakoshi, Yasuo; Yamakoshi, Fumiko; Hu, Jan C-C; Simmer, James P

    2011-12-01

    Kallikrein-related peptidase 4 (KLK4) is a glycosylated serine protease that functions in the maturation (hardening) of dental enamel. Pig and mouse KLK4 contain three potential N-glycosylation sites. We isolated KLK4 from developing pig and mouse molars and characterized their N-glycosylations. N-glycans were enzymatically released by digestion with N-glycosidase F and fluorescently labeled with 2-aminobenzoic acid. Normal-phase high-performance liquid chromatography (NP-HPLC) revealed N-glycans with no, or with one, two, or three sialic acid attachments in pig KLK4 and with no, or with one or two sialic acid attachments in mouse KLK4. The labeled N-glycans were digested with sialidase to generate the asialo N-glycan cores that were fractionated by reverse-phase HPLC, and their retention times were compared with similarly labeled glycan standards. The purified cores were characterized by mass spectrometric and monosaccharide composition analyses. We determined that pig and mouse KLK4 have NA2 and NA2F biantennary N-glycan cores. The pig triantennary core is NA3. The mouse triantennary core is NA3 with a fucose connected by an α1-6 linkage, indicating that it is attached to the first N-acetyglucosamine (NA3F). We conclude that pig KLK4 has NA2, NA2F, and NA3 N-glycan cores with no, or with one, two, or three sialic acids. Mouse KLK4 has NA2, NA2F, and NA3F N-glycan cores with no, or with one or two sialic acids. © 2011 Eur J Oral Sci.

  11. Glycosylation Alters Dimerization Properties of a Cell-surface Signaling Protein, Carcinoembryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1)*

    Science.gov (United States)

    Zhuo, You; Yang, Jeong-Yeh; Moremen, Kelley W.; Prestegard, James H.

    2016-01-01

    Human carcinoembryonic antigen-related cell adhesion molecule 1 (C?/Au: EACAM1) is a cell-surface signaling molecule involved in cell adhesion, proliferation, and immune response. It is also implicated in cancer angiogenesis, progression, and metastasis. This diverse set of effects likely arises as a result of the numerous homophilic and heterophilic interactions that CEACAM1 can have with itself and other molecules. Its N-terminal Ig variable (IgV) domain has been suggested to be a principal player in these interactions. Previous crystal structures of the β-sandwich-like IgV domain have been produced using Escherichia coli-expressed material, which lacks native glycosylation. These have led to distinctly different proposals for dimer interfaces, one involving interactions of ABED β-strands and the other involving GFCC′C″ β-strands, with the former burying one prominent glycosylation site. These structures raise questions as to which form may exist in solution and what the effect of glycosylation may have on this form. Here, we use NMR cross-correlation measurements to examine the effect of glycosylation on CEACAM1-IgV dimerization and use residual dipolar coupling (RDC) measurements to characterize the solution structure of the non-glycosylated form. Our findings demonstrate that even addition of a single N-linked GlcNAc at potential glycosylation sites inhibits dimer formation. Surprisingly, RDC data collected on E. coli expressed material in solution indicate that a dimer using the non-glycosylated GFCC′C″ interface is preferred even in the absence of glycosylation. The results open new questions about what other factors may facilitate dimerization of CEACAM1 in vivo, and what roles glycosylation may play in heterophylic interactions. PMID:27471271

  12. Analysis of urinary PSA glycosylation is not indicative of high-risk prostate cancer.

    Science.gov (United States)

    Barrabés, Sílvia; Llop, Esther; Ferrer-Batallé, Montserrat; Ramírez, Manel; Aleixandre, Rosa N; Perry, Antoinette S; de Llorens, Rafael; Peracaula, Rosa

    2017-07-01

    The levels of core fucosylation and α2,3-linked sialic acid in serum Prostate Specific Antigen (PSA), using the lectins Pholiota squarrosa lectin (PhoSL) and Sambucus nigra agglutinin (SNA), can discriminate between Benign Prostatic Hyperplasia (BPH) and indolent prostate cancer (PCa) from aggressive PCa. In the present work we evaluated whether these glycosylation determinants could also be altered in urinary PSA obtained after digital rectal examination (DRE) and could also be useful for diagnosis determinations. For this purpose, α2,6-sialic acid and α1,6-fucose levels of urinary PSA from 53 patients, 18 biopsy-negative and 35 PCa patients of different aggressiveness degree, were analyzed by sandwich ELLA (Enzyme Linked Lectin Assay) using PhoSL and SNA. Changes in the levels of specific glycosylation determinants, that in serum PSA samples were indicative of PCa aggressiveness, were not found in PSA from DRE urine samples. Although urine is a simpler matrix for analyzing PSA glycosylation compared to serum, an immunopurification step was necessary to specifically detect the glycans on the PSA molecule. Those specific glycosylation determinants on urinary PSA were however not useful to improve PCa diagnosis. This could be probably due to the low proportion of PSA from the tumor in urine samples, which precludes the identification of aberrantly glycosylated PSA. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Protein glycosylation in cancers and its potential therapeutic applications in neuroblastoma

    Directory of Open Access Journals (Sweden)

    Wan-Ling Ho

    2016-09-01

    Full Text Available Abstract Glycosylation is the most complex post-translational modification of proteins. Altered glycans on the tumor- and host-cell surface and in the tumor microenvironment have been identified to mediate critical events in cancer pathogenesis and progression. Tumor-associated glycan changes comprise increased branching of N-glycans, higher density of O-glycans, generation of truncated versions of normal counterparts, and generation of unusual forms of terminal structures arising from sialylation and fucosylation. The functional role of tumor-associated glycans (Tn, sTn, T, and sLea/x is dependent on the interaction with lectins. Lectins are expressed on the surface of immune cells and endothelial cells or exist as extracellular matrix proteins and soluble adhesion molecules. Expression of tumor-associated glycans is involved in the dysregulation of glycogenes, which mainly comprise glycosyltransferases and glycosidases. Furthermore, genetic and epigenetic mechanisms on many glycogenes are associated with malignant transformation. With better understanding of all aspects of cancer-cell glycomics, many tumor-associated glycans have been utilized for diagnostic, prognostic, and therapeutic purposes. Glycan-based therapeutics has been applied to cancers from breast, lung, gastrointestinal system, melanomas, and lymphomas but rarely to neuroblastomas (NBs. The success of anti-disialoganglioside (GD2, a glycolipid antigen antibodies sheds light on glycan-based therapies for NB and also suggests the possibility of protein glycosylation-based therapies for NB. This review summarizes our understanding of cancer glycobiology with a focus of how protein glycosylation and associated glycosyltransferases affect cellular behaviors and treatment outcome of various cancers, especially NB. Finally, we highlight potential applications of glycosylation in drug and cancer vaccine development for NB.

  14. Role of Cytokine-Induced Glycosylation Changes in Regulating Cell Interactions and Cell Signaling in Inflammatory Diseases and Cancer

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    Justine H. Dewald

    2016-11-01

    Full Text Available Glycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of biological functions including cell-cell and cell-substrate interactions, bacterial adhesion, cell immunogenicity and cell signaling. Alterations of glycosylation are observed in number of diseases such as cancer and chronic inflammation. In that context, pro-inflammatory cytokines have been shown to modulate cell surface glycosylation by regulating the expression of glycosyltransferases involved in the biosynthesis of carbohydrate chains. These changes in cell surface glycosylation are also known to regulate cell signaling and could contribute to disease pathogenesis. This review summarizes our current knowledge of the glycosylation changes induced by pro-inflammatory cytokines, with a particular focus on cancer and cystic fibrosis, and their consequences on cell interactions and signaling.

  15. Quantification of the N-glycosylated secretome by super-SILAC during breast cancer progression and in human blood Samples

    DEFF Research Database (Denmark)

    Boersema, P.J.; Geiger, T.; Wiśniewski, J.R.

    2013-01-01

    Cells secrete a large number of proteins to communicate with their surroundings. Furthermore, plasma membrane proteins and intracellular proteins can be released into the extracellular space by regulated or non-regulated processes. Here, we profiled the supernatant of 11 cell lines....... In total, 1398 unique N-glycosylation sites were identified and quantified. Enriching for N-glycosylated peptides focused the analysis on classically secreted and membrane proteins. N-glycosylated secretome profiles correctly clustered the different cell lines to their respective cancer stage, suggesting...

  16. N-glycosylation of colorectal cancer tissues: a liquid chromatography and mass spectrometry-based investigation.

    Science.gov (United States)

    Balog, Crina I A; Stavenhagen, Kathrin; Fung, Wesley L J; Koeleman, Carolien A; McDonnell, Liam A; Verhoeven, Aswin; Mesker, Wilma E; Tollenaar, Rob A E M; Deelder, André M; Wuhrer, Manfred

    2012-09-01

    Colorectal cancer is the third most common cancer worldwide with an annual incidence of ~1 million cases and an annual mortality rate of ~655,000 individuals. There is an urgent need for identifying novel targets to develop more sensitive, reliable, and specific tests for early stage detection of colon cancer. Post-translational modifications are known to play an important role in cancer progression and immune surveillance of tumors. In the present study, we compared the N-glycan profiles from 13 colorectal cancer tumor tissues and corresponding control colon tissues. The N-glycans were enzymatically released, purified, and labeled with 2-aminobenzoic acid. Aliquots were profiled by hydrophilic interaction liquid chromatography (HILIC-HPLC) with fluorescence detection and by negative mode MALDI-TOF-MS. Using partial least squares discriminant analysis to investigate the N-glycosylation changes in colorectal cancer, an excellent separation and prediction ability were observed for both HILIC-HPLC and MALDI-TOF-MS data. For structure elucidation, information from positive mode ESI-ion trap-MS/MS and negative mode MALDI-TOF/TOF-MS was combined. Among the features with a high separation power, structures containing a bisecting GlcNAc were found to be decreased in the tumor, whereas sulfated glycans, paucimannosidic glycans, and glycans containing a sialylated Lewis type epitope were shown to be increased in tumor tissues. In addition, core-fucosylated high mannose N-glycans were detected in tumor samples. In conclusion, the combination of HILIC and MALDI-TOF-MS profiling of N-glycans with multivariate statistical analysis demonstrated its potential for identifying N-glycosylation changes in colorectal cancer tissues and provided new leads that might be used as candidate biomarkers.

  17. DMBT1 expression and glycosylation during the adenoma-carcinoma sequence in colorectal cancer

    DEFF Research Database (Denmark)

    Robbe, C; Paraskeva, C; Mollenhauer, J

    2005-01-01

    , location and its mode of secretion during malignant transformation in colorectal cancer. Using human colorectal PC/AA cell lines and tissue sections from individual patients, we have examined the expression of DMBT1 and its glycosylation in the adenoma-carcinoma sequence leading to the adenocarcinoma......The gene DMBT1 (deleted in malignant brain tumour-1) has been proposed to play a role in brain and epithelial cancer, but shows unusual features for a classical tumour-suppressor gene. On the one hand, DMBT1 has been linked to mucosal protection, whereas, on the other, it potentially plays a role...... in epithelial differentiation. Thus its function in a particular tissue is of mechanistic importance for its role in cancer. Because the former function requires secretion to the lumen and the latter function may depend on its presence in the extracellular matrix, we decided to investigate DMBT1 expression...

  18. Expression of cancer-associated simple mucin-type O-glycosylated antigens in parasites.

    Science.gov (United States)

    Osinaga, Eduardo

    2007-01-01

    Simple mucin-type O-glycan structures, such as Tn, TF, sialyl-Tn and Tk antigens, are among of the most specific human cancer-associated structures. These antigens are involved in several types of receptor-ligand interactions, and they are potential targets for immunotherapy. In the last few years several simple mucin-type O-glycan antigens were identified in different species belonging to the main two helminth parasite phyla, and sialyl-Tn bearing glycoproteins were detected in Trypanosoma cruzi. These results are of interest to understand new aspects in parasite glycoimmunology and may help identify new biological characteristics of parasites as well of the host-parasite relationship. Considering that different groups reported a negative correlation between certain parasite infections and cancer development, we could hypothesize that simple mucin-type O-glycosylated antigens obtained from parasites could be good potential targets for cancer immunotherapy.

  19. Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN.

    Science.gov (United States)

    Menck, Kerstin; Scharf, Christian; Bleckmann, Annalen; Dyck, Lydia; Rost, Ulrike; Wenzel, Dirk; Dhople, Vishnu M; Siam, Laila; Pukrop, Tobias; Binder, Claudia; Klemm, Florian

    2015-04-01

    Tumor cells secrete not only a variety of soluble factors, but also extracellular vesicles that are known to support the establishment of a favorable tumor niche by influencing the surrounding stroma cells. Here we show that tumor-derived microvesicles (T-MV) also directly influence the tumor cells by enhancing their invasion in a both autologous and heterologous manner. Neither the respective vesicle-free supernatant nor MV from benign mammary cells mediate invasion. Uptake of T-MV is essential for the proinvasive effect. We further identify the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) as a marker for proinvasive MV. EMMPRIN is also present at high levels on MV from metastatic breast cancer patients in vivo. Anti-EMMPRIN strategies, such as MV deglycosylation, gene knockdown, and specific blocking peptides, inhibit MV-induced invasion. Interestingly, the effect of EMMPRIN-bearing MV is not mediated by matrix metalloproteinases but by activation of the p38/MAPK signaling pathway in the tumor cells. In conclusion, T-MV stimulate cancer cell invasion via a direct feedback mechanism dependent on highly glycosylated EMMPRIN. © The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.

  20. Preventing E-cadherin aberrant N-glycosylation at Asn-554 improves its critical function in gastric cancer

    Science.gov (United States)

    Carvalho, S; Catarino, TA; Dias, AM; Kato, M; Almeida, A; Hessling, B; Figueiredo, J; Gärtner, F; Sanches, JM; Ruppert, T; Miyoshi, E; Pierce, M; Carneiro, F; Kolarich, D; Seruca, R; Yamaguchi, Y; Taniguchi, N; Reis, CA; Pinho, SS

    2016-01-01

    E-cadherin is a central molecule in the process of gastric carcinogenesis and its posttranslational modifications by N-glycosylation have been described to induce a deleterious effect on cell adhesion associated with tumor cell invasion. However, the role that site-specific glycosylation of E-cadherin has in its defective function in gastric cancer cells needs to be determined. Using transgenic mice models and human clinical samples, we demonstrated that N-acetylglucosaminyltransferase V (GnT-V)-mediated glycosylation causes an abnormal pattern of E-cadherin expression in the gastric mucosa. In vitro models further indicated that, among the four potential N-glycosylation sites of E-cadherin, Asn-554 is the key site that is selectively modified with β1,6 GlcNAc-branched N-glycans catalyzed by GnT-V. This aberrant glycan modification on this specific asparagine site of E-cadherin was demonstrated to affect its critical functions in gastric cancer cells by affecting E-cadherin cellular localization, cis-dimer formation, molecular assembly and stability of the adherens junctions and cell–cell aggregation, which was further observed in human gastric carcinomas. Interestingly, manipulating this site-specific glycosylation, by preventing Asn-554 from receiving the deleterious branched structures, either by a mutation or by silencing GnT-V, resulted in a protective effect on E-cadherin, precluding its functional dysregulation and contributing to tumor suppression. PMID:26189796

  1. Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis

    DEFF Research Database (Denmark)

    Blixt, Ola; Bueti, Deanna; Burford, Brian

    2011-01-01

    associated glycoforms of MUC1 in a proportion of early breast cancer patients (54/198). Five positive sera were selected for detailed definition of the reactive epitopes using on chip glycosylation technology and a panel of glycopeptides based on a single MUC1 tandem repeat carrying specific glycans...

  2. Cancer cell spheroids are a better screen for the photodynamic efficiency of glycosylated photosensitizers.

    Directory of Open Access Journals (Sweden)

    Patrícia M R Pereira

    Full Text Available Photodynamic Therapy (PDT relies on the use of non-toxic photosensitizers that are locally and selectively activated by light to induce cell death or apoptosis through reactive oxygen species generation. The conjugation of porphyrinoids with sugars that target cancer is increasingly viewed as an effective way to increase the selectivity of PDT. To date, in vitro PDT efficacy is mostly screened using two-dimensional monolayer cultures. Compared to monolayer cultures, three-dimensional spheroid cultures have unique spatial distributions of nutrients, metabolites, oxygen and signalling molecules; therefore better mimic in vivo conditions. We obtained 0.05 mm3 spheroids with four different human tumor cell lines (HCT-116, MCF-7, UM-UC-3 and HeLa with appropriate sizes for screening PDT agents. We observed that detachment from monolayer culture and growth as tumor spheroids was accompanied by changes in glucose metabolism, endogenous ROS levels, galectin-1 and glucose transporter GLUT1 protein levels. We compared the phototoxic responses of a porphyrin conjugated with four glucose molecules (PorGlu4 in monolayer and spheroid cultures. The uptake and phototoxicity of PorGlu4 is highly dependent on the monolayer versus spheroid model used and on the different levels of GLUT1 protein expressed by these in vitro platforms. This study demonstrates that HCT-116, MCF-7, UM-UC-3 and HeLa spheroids afford a more rational platform for the screening of new glycosylated-photosensitizers compared to monolayer cultures of these cancer cells.

  3. Glycosylation Engineering

    DEFF Research Database (Denmark)

    Clausen, Henrik; Wandall, Hans H.; Steentoft, Catharina

    2017-01-01

    Knowledge of the cellular pathways of glycosylation across phylogeny provides opportunities for designing glycans via genetic engineering in a wide variety of cell types including bacteria, fungi, plant cells, and mammalian cells. The commercial demand for glycosylation engineering is broad......, including production of biological therapeutics with defined glycosylation (Chapter 57). This chapter describes how knowledge of glycan structures and their metabolism (Parts I–III of this book) has led to the current state of glycosylation engineering in different cell types. Perspectives for rapid...

  4. Immunolocalisation of members of the polypeptide N-acetylgalactosaminyl transferase (ppGalNAc-T) family is consistent with biologically relevant altered cell surface glycosylation in breast cancer

    DEFF Research Database (Denmark)

    Brooks, Susan A; Carter, Tracey M; Bennett, Eric P

    2007-01-01

    understood, may mediate the synthesis of varied glycoforms of cellular proteins with different biological activities. Disruptions in glycosylation are a common feature of cancer and may have functional significance. Immunocytochemistry with confocal scanning laser microscopy was employed to detect members...... of the ppGalNAc-T family, ppGalNAc-T1, -T2, -T3, -T4 and -T6 in a range of breast cell lines. The cells were chosen to represent a range of phenotypes from 'normal'/benign (HMT 3,522), primary, non-metastatic breast cancer (BT 474), to aggressive, metastatic breast cancer (ZR75-1, T47D, MCF-7, DU 4...... tightly restricted ppGalNAc-T's may result in initiation of O-linked glycosylation at normally unoccupied potential glycosylation sites leading to altered glycoforms of proteins with changed biological activity which may contribute to the pathogenesis of cancer....

  5. Thermophilic and thermoacidophilic glycosylation genes and enzymes from Alicyclobacillus acidocaldarius and related organisms, methods

    Science.gov (United States)

    Thompson, David N.; Apel, William A.; Thompson, Vicki S.; Reed, David W.; Lacey, Jeffrey A.

    2016-01-12

    Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for glycosylating and/or post-translationally modifying proteins using isolated and/or purified polypeptides and nucleic acid sequences from Alicyclobacillus acidocaldarius.

  6. A compound heterozygous mutation in DPAGT1 results in a congenital disorder of glycosylation with a relatively mild phenotype

    NARCIS (Netherlands)

    Iqbal, Z.; Shahzad, M.; Vissers, L.E.L.M.; Scherpenzeel, M. van; Gilissen, C.; Razzaq, A.; Zahoor, M.Y.; Khan, S.N.; Kleefstra, T.; Veltman, J.A.; Brouwer, A.P.M. de; Lefeber, D.J.; Bokhoven, H. van; Riazuddin, S.

    2013-01-01

    Congenital disorders of glycosylation (CDG) are a large group of recessive multisystem disorders caused by impaired protein or lipid glycosylation. The CDG-I subgroup is characterized by protein N-glycosylation defects originating in the endoplasmic reticulum. The genetic defect is known for 17

  7. Integrated proteomic and N-glycoproteomic analyses of doxorubicin sensitive and resistant ovarian cancer cells reveal glycoprotein alteration in protein abundance and glycosylation

    Science.gov (United States)

    Hou, Junjie; Zhang, Chengqian; Xue, Peng; Wang, Jifeng; Chen, Xiulan; Guo, Xiaojing; Yang, Fuquan

    2017-01-01

    Ovarian cancer is one of the most common cancer among women in the world, and chemotherapy remains the principal treatment for patients. However, drug resistance is a major obstacle to the effective treatment of ovarian cancers and the underlying mechanism is not clear. An increased understanding of the mechanisms that underline the pathogenesis of drug resistance is therefore needed to develop novel therapeutics and diagnostic. Herein, we report the comparative analysis of the doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI/ADR-RES cells using integrated global proteomics and N-glycoproteomics. A total of 1525 unique N-glycosite-containing peptides from 740 N-glycoproteins were identified and quantified, of which 253 N-glycosite-containing peptides showed significant change in the NCI/ADR-RES cells. Meanwhile, stable isotope labeling by amino acids in cell culture (SILAC) based comparative proteomic analysis of the two ovarian cancer cells led to the quantification of 5509 proteins. As about 50% of the identified N-glycoproteins are low-abundance membrane proteins, only 44% of quantified unique N-glycosite-containing peptides had corresponding protein expression ratios. The comparison and calibration of the N-glycoproteome versus the proteome classified 14 change patterns of N-glycosite-containing peptides, including 8 up-regulated N-glycosite-containing peptides with the increased glycosylation sites occupancy, 35 up-regulated N-glycosite-containing peptides with the unchanged glycosylation sites occupancy, 2 down-regulated N-glycosite-containing peptides with the decreased glycosylation sites occupancy, 46 down-regulated N-glycosite-containing peptides with the unchanged glycosylation sites occupancy. Integrated proteomic and N-glycoproteomic analyses provide new insights, which can help to unravel the relationship of N-glycosylation and multidrug resistance (MDR), understand the mechanism of MDR, and discover the new diagnostic and

  8. Alterations in expressed prostate secretion-urine PSA N-glycosylation discriminate prostate cancer from benign prostate hyperplasia.

    Science.gov (United States)

    Jia, Gaozhen; Dong, Zhenyang; Sun, Chenxia; Wen, Fuping; Wang, Haifeng; Guo, Huaizu; Gao, Xu; Xu, Chuanliang; Xu, Chuanliang; Yang, Chenghua; Sun, Yinghao

    2017-09-29

    The prostate specific antigen (PSA) test is widely used for early diagnosis of prostate cancer (PCa). However, its limited sensitivity has led to over-diagnosis and over-treatment of PCa. Glycosylation alteration is a common phenomenon in cancer development. Different PSA glycan subforms have been proposed as diagnostic markers to better differentiate PCa from benign prostate hyperplasia (BPH). In this study, we purified PSA from expressed prostate secretions (EPS)-urine samples from 32 BPH and 30 PCa patients and provided detailed PSA glycan profiles in Chinese population. We found that most of the PSA glycans from EPS-urine were complex type biantennary glycans. We observed two major patterns in PSA glycan profiles. Overall there was no distinct separation of PSA glycan profiles between BPH and PCa patients. However, we detected a significant increase of glycan FA2 and FM5A2G2S1 in PCa when compared with BPH patients. Furthermore, we observed that the composition of FA2 glycan increased significantly in advanced PCa with Gleason score ≥8, which potentially could be translated to clinic as a marker for aggressive PCa.

  9. Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers

    NARCIS (Netherlands)

    Lauc, G.; Huffman, J.E.; Pucic, M.; Zgaga, L.; Adamczyk, B.; Muzinic, A.; Novokmet, M.; Polasek, O.; Gornik, O.; Kristic, J.; Keser, T.; Vitart, V.; Scheijen, B.; Uh, H.W.; Molokhia, M.; Patrick, A.L.; McKeigue, P.; Kolcic, I.; Lukic, I.K.; Swann, O.; Leeuwen, F.N. van; Ruhaak, L.R.; Houwing-Duistermaat, J.J.; Slagboom, P.E.; Beekman, M.; Craen, A.J. de; Deelder, A.M.; Zeng, Q.; Wang, W.; Hastie, N.D.; Gyllensten, U.; Wilson, J.F.; Wuhrer, M.; Wright, A.F.; Rudd, P.M.; Hayward, C.; Aulchenko, Y.; Campbell, H.; Rudan, I.

    2013-01-01

    Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative

  10. Glycosylation-related gene expression in HT29-MTX-E12 cells upon infection by Helicobacter pylori.

    Science.gov (United States)

    Cairns, Michael T; Gupta, Ananya; Naughton, Julie A; Kane, Marian; Clyne, Marguerite; Joshi, Lokesh

    2017-10-07

    To identify glycosylation-related genes in the HT29 derivative cell line, HT29-MTX-E12, showing differential expression on infection with Helicobacter pylori ( H. pylori ). Polarised HT29-MTX-E12 cells were infected for 24 h with H. pylori strain 26695. After infection RNA was isolated from both infected and non-infected host cells. Sufficient infections were carried out to provide triplicate samples for microarray analysis and for qRT-PCR analysis. RNA was isolated and hybridised to Affymetrix arrays. Analysis of microarray data identified genes significantly differentially expressed upon infection. Genes were grouped into gene ontology functional categories. Selected genes associated with host glycan structure (glycosyltransferases, hydrolases, lectins, mucins) were validated by real-time qRT-PCR analysis. Infection of host cells was confirmed by the isolation of live bacteria after 24 h incubation and by PCR amplification of bacteria-specific genes from the host cell RNA. H. pylori do not survive incubation under the adopted culture conditions unless they associate with the adherent mucus layer of the host cell. Microarray analysis identified a total of 276 genes that were significantly differentially expressed ( P < 0.05) upon H. pylori infection and where the fold change in expression was greater than 2. Six of these genes are involved in glycosylation-related processes. Real-time qRT-PCR demonstrated significant downregulation (1.8-fold, P < 0.05) of the mucin MUC20. REG4 was heavily expressed and significantly downregulated (3.1-fold, P < 0.05) upon infection. Gene ontology analysis was consistent with previous studies on H. pylori infection. Gene expression data suggest that infection with H. pylori causes a decrease in glycan synthesis, resulting in shorter and simpler glycan structures.

  11. The relative contribution of mannose salvage pathways to glycosylation in PMI-deficient mouse embryonic fibroblast cells.

    Science.gov (United States)

    Fujita, Naonobu; Tamura, Ayako; Higashidani, Aya; Tonozuka, Takashi; Freeze, Hudson H; Nishikawa, Atsushi

    2008-02-01

    Mannose for mammalian glycan biosynthesis can be imported directly from the medium, derived from glucose or salvaged from endogenous or external glycans. All pathways must generate mannose 6-phosphate, the activated form of mannose. Imported or salvaged mannose is directly phosphorylated by hexokinase, whereas fructose 6-phosphate from glucose is converted to mannose 6-phosphate by phosphomannose isomerase (PMI). Normally, PMI provides the majority of mannose for glycan synthesis. To assess the contribution of PMI-independent pathways, we used PMI-null fibroblasts to study N-glycosylation of DNase I, a highly sensitive indicator protein. In PMI-null cells, imported mannose and salvaged mannose make a significant contribution to N-glycosylation. When these cells were grown in mannose-free medium along with the mannosidase inhibitor, swainsonine, to block the salvage pathways, N-glycosylation of DNase I was almost completely eliminated. Adding approximately 13 microm mannose to the medium completely restored normal glycosylation. Treatment with bafilomycin A(1), an inhibitor of lysosomal acidification, also markedly reduced N-glycosylation of DNase I, but in this case only 8 microm mannose was required to restore full glycosylation, indicating that a nonlysosomal source of mannose made a significant contribution. Glycosylation levels were greatly also reduced in glycoconjugate-free medium, when endosomal membrane trafficking was blocked by expression of a mutant SKD1. From these data, we conclude that PMI-null cells can salvage mannose from both endogenous and external glycoconjugates via lysosomal and nonlysosomal degradation pathways.

  12. Investigations on aberrant glycosylation of glycosphingolipids in colorectal cancer tissues using liquid chromatography and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS).

    Science.gov (United States)

    Holst, Stephanie; Stavenhagen, Kathrin; Balog, Crina I A; Koeleman, Carolien A M; McDonnell, Liam M; Mayboroda, Oleg A; Verhoeven, Aswin; Mesker, Wilma E; Tollenaar, Rob A E M; Deelder, André M; Wuhrer, Manfred

    2013-11-01

    Cancer is a leading cause of death and alterations of glycosylation are characteristic features of malignant cells. Colorectal cancer is one of the most common cancers and its exact causes and biology are not yet well understood. Here, we compared glycosylation profiles of colorectal tumor tissues and corresponding control tissues of 13 colorectal cancer patients to contribute to the understanding of this cancer. Using MALDI-TOF(/TOF)-MS and 2-dimensional LC-MS/MS we characterized enzymatically released and 2-aminobenzoic acid labeled glycans from glycosphingolipids. Multivariate data analysis revealed significant differences between tumor and corresponding control tissues. Main discriminators were obtained, which represent the overall alteration in glycosylation of glycosphingolipids during colorectal cancer progression, and these were found to be characterized by (1) increased fucosylation, (2) decreased acetylation, (3) decreased sulfation, (4) reduced expression of globo-type glycans, as well as (5) disialyl gangliosides. The findings of our current research confirm former reports, and in addition expand the knowledge of glycosphingolipid glycosylation in colorectal cancer by revealing new glycans with discriminative power and characteristic, cancer-associated glycosylation alterations. The obtained discriminating glycans can contribute to progress the discovery of biomarkers to improve diagnostics and patient treatment.

  13. Investigations on Aberrant Glycosylation of Glycosphingolipids in Colorectal Cancer Tissues Using Liquid Chromatography and Matrix-Assisted Laser Desorption Time-of-Flight Mass Spectrometry (MALDI-TOF-MS)*

    Science.gov (United States)

    Holst, Stephanie; Stavenhagen, Kathrin; Balog, Crina I. A.; Koeleman, Carolien A. M.; McDonnell, Liam M.; Mayboroda, Oleg A.; Verhoeven, Aswin; Mesker, Wilma E.; Tollenaar, Rob A. E. M.; Deelder, André M.; Wuhrer, Manfred

    2013-01-01

    Cancer is a leading cause of death and alterations of glycosylation are characteristic features of malignant cells. Colorectal cancer is one of the most common cancers and its exact causes and biology are not yet well understood. Here, we compared glycosylation profiles of colorectal tumor tissues and corresponding control tissues of 13 colorectal cancer patients to contribute to the understanding of this cancer. Using MALDI-TOF(/TOF)-MS and 2-dimensional LC-MS/MS we characterized enzymatically released and 2-aminobenzoic acid labeled glycans from glycosphingolipids. Multivariate data analysis revealed significant differences between tumor and corresponding control tissues. Main discriminators were obtained, which represent the overall alteration in glycosylation of glycosphingolipids during colorectal cancer progression, and these were found to be characterized by (1) increased fucosylation, (2) decreased acetylation, (3) decreased sulfation, (4) reduced expression of globo-type glycans, as well as (5) disialyl gangliosides. The findings of our current research confirm former reports, and in addition expand the knowledge of glycosphingolipid glycosylation in colorectal cancer by revealing new glycans with discriminative power and characteristic, cancer-associated glycosylation alterations. The obtained discriminating glycans can contribute to progress the discovery of biomarkers to improve diagnostics and patient treatment. PMID:23878401

  14. Improvement of Prostate Cancer Diagnosis by Detecting PSA Glycosylation-Specific Changes.

    Science.gov (United States)

    Llop, Esther; Ferrer-Batallé, Montserrat; Barrabés, Sílvia; Guerrero, Pedro Enrique; Ramírez, Manel; Saldova, Radka; Rudd, Pauline M; Aleixandre, Rosa N; Comet, Josep; de Llorens, Rafael; Peracaula, Rosa

    2016-01-01

    New markers based on PSA isoforms have recently been developed to improve prostate cancer (PCa) diagnosis. However, novel approaches are still required to differentiate aggressive from non-aggressive PCa to improve decision making for patients. PSA glycoforms have been shown to be differentially expressed in PCa. In particular, changes in the extent of core fucosylation and sialylation of PSA N-glycans in PCa patients compared to healthy controls or BPH patients have been reported. The objective of this study was to determine these specific glycan structures in serum PSA to analyze their potential value as markers for discriminating between BPH and PCa of different aggressiveness. In the present work, we have established two methodologies to analyze the core fucosylation and the sialic acid linkage of PSA N-glycans in serum samples from BPH (29) and PCa (44) patients with different degrees of aggressiveness. We detected a significant decrease in the core fucose and an increase in the α2,3-sialic acid percentage of PSA in high-risk PCa that differentiated BPH and low-risk PCa from high-risk PCa patients. In particular, a cut-off value of 0.86 of the PSA core fucose ratio, could distinguish high-risk PCa patients from BPH with 90% sensitivity and 95% specificity, with an AUC of 0.94. In the case of the α2,3-sialic acid percentage of PSA, the cut-off value of 30% discriminated between high-risk PCa and the group of BPH, low-, and intermediate-risk PCa with a sensitivity and specificity of 85.7% and 95.5%, respectively, with an AUC of 0.97. The latter marker exhibited high performance in differentiating between aggressive and non-aggressive PCa and has the potential for translational application in the clinic.

  15. Cancer-related anemia

    International Nuclear Information System (INIS)

    Abdel-Rzaeq, Hikmat N.

    2004-01-01

    Anemia is the most common hematological abnormality in cancer patients is often under-recognized and undertreated. The pathogenesis of cancer anemia is complex and most of time multifactorial; involving factors related to the tumor itself or its therapy. While anemia can be present in a wide range of symptoms, involing almost every organ, it is beleived that it contributes much to cancer-related-fatigue, one of the most common symptoms in cancer patients. In addition there is increasing evidence to suggest that anemia is an independent factor adversely affecting tumor reponse and patient survival. While blood transfusion was the only option to treat cancer related anemia, the use of recombinant human erythropoietin (rHuEPO) is becomig the new standard of care, more so with the recent studies demonstrating the feasibility of a sigle weekly injection .Things are even getting better with the recent approval of a new form of rHuEPO; Darbepoetin an analogue with a 3-fold longer half-life. In addition to its effects in raising homoglobin, several well controlled studies demonstrated decrease in transfusion requirementsand better qualify of life assessed objectively using standard assesments scales. (author)

  16. Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1

    DEFF Research Database (Denmark)

    Gils, Ann; Pedersen, Katrine Egelund; Skottrup, Peter

    2003-01-01

    The serpin plasminogen activator inhibitor-1 (PAI-1) is a potential target for anti-thrombotic and anti-cancer therapy. PAI-1 has 3 potential sites for N-linked glycosylation. We demonstrate here that PAI-1 expressed recombinantly or naturally by human cell lines display a heterogeneous glycosyla......The serpin plasminogen activator inhibitor-1 (PAI-1) is a potential target for anti-thrombotic and anti-cancer therapy. PAI-1 has 3 potential sites for N-linked glycosylation. We demonstrate here that PAI-1 expressed recombinantly or naturally by human cell lines display a heterogeneous...... with the glycosylation sites could be excluded as explanation for the differential reactivity. The latency transition of non-glycosylated, but not of glycosylated PAI-1, was strongly accelerated by a non-ionic detergent. The different biochemical properties of glycosylated and non-glycosylated PAI-1 depended...

  17. Closely related glycosylation patterns of recombinant human IL-2 expressed in a CHO cell line and natural IL-2

    International Nuclear Information System (INIS)

    Vita, N.; Magazin, M.; Marchese, E.; Lupker, J.; Ferrara, P.

    1990-01-01

    We report here the study of the glycosylation pattern of human recombinant (r) IL2 expressed in a Chinese hamster ovary (CHO) cell line. The human rIL2 secreted by this high-producing recombinant CHO cell line was metabolically radiolabelled with [35S]-methionine, or with [3H]-glucosamine and [3H]-galactose, purified to homogeneity, and then characterized. The electrophoretic analysis of the [35S]-methionine-labelled proteins present in the culture medium of the CHO cell line showed that the rIL2 represents approximately 12% of the total secreted proteins. Furthermore, pulse-chase experiments showed that the glycosylated rIL2 is synthesized and secreted within 30 min. The point of attachment and the structure of the carbohydrate moiety of the rIL2 was determined by: amino-terminal sequencing and fingerprint analysis of the 3H-labelled rIL2, mass spectroscopy of the amino-terminal tryptic octapeptide, and carbohydrate analysis after enzymatic (Vibrio cholerae neuraminidase and Aspergillus oryzae beta-galactosidase) or sulfuric acid hydrolysis. The results indicate that the recombinant protein possesses a sugar moiety O-linked to the threonine residue at position 3 of the polypeptide chain, and that sialic acid, galactose and N-acetyl galactosamine are components of this carbohydrate moiety. Taken together these results suggest that the recombinant molecule is identical to natural IL2

  18. Cancer-Related Fatigue in Cancer Survivorship.

    Science.gov (United States)

    Ebede, Chidinma C; Jang, Yongchang; Escalante, Carmen P

    2017-11-01

    Cancer-related fatigue (CRF) significantly interferes with usual functioning because of the distressing sense of physical, emotional, and cognitive exhaustion. Assessment of CRF is important and should be performed during the initial cancer diagnosis, throughout cancer treatment, and after treatment using a fatigue scoring scale (mild-severe). The general approach to CRF management applies to cancer survivors at all fatigue levels and includes education, counseling, and other strategies. Nonpharmacologic interventions include psychosocial interventions, exercise, yoga, physically based therapy, dietary management, and sleep therapy. Pharmacologic interventions include psychostimulants. Antidepressants may also benefit when CRF is accompanied by depression. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. N-glycosylation of asparagine 8 regulates surface expression of major histocompatibility complex class I chain-related protein A (MICA) alleles dependent on threonine 24

    DEFF Research Database (Denmark)

    Pedersen, Maiken Mellergaard; Skovbakke, Sarah Line; Schneider, Christine L.

    2014-01-01

    for cell-surface expression and sought to identify the essential residues. We found that a single N-glycosylation site (N8) was important for MICA018 surface expression. The frequently expressed MICA allele 008, with an altered transmembrane and intracellular domain, was not affected by mutation of this N......-glycosylation site. Mutational analysis revealed that a single amino acid (T24) in the extracellular domain of MICA018 was essential for the N-glycosylation dependency, while the intracellular domain was not involved. The HHV7 immunoevasin, U21, was found to inhibit MICA018 surface expression by affecting N......-glycosylation and the retention was rescued by T24A substitution. Our study reveals N-glycosylation as an allele-specific regulatory mechanism important for regulation of surface expression of MICA018 and we pinpoint the residues essential for this N-glycosylation dependency. In addition we show that this regulatory mechanism...

  20. Diagnosis and activity assessment of immunoglobulin A nephropathy: current perspectives on noninvasive testing with aberrantly glycosylated immunoglobulin A-related biomarkers

    Directory of Open Access Journals (Sweden)

    Suzuki Y

    2014-10-01

    Full Text Available Yusuke Suzuki,1 Hitoshi Suzuki,1 Yuko Makita,1 Akiko Takahata,1 Keiko Takahashi,1 Masahiro Muto,1 Yohei Sasaki,1 Atikemu Kelimu,1 Keiichi Matsuzaki,2 Hiroyuki Yanagawa,1 Keiko Okazaki,1 Yasuhiko Tomino1 1Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, Tokyo, 2Kyoto University Health Service, Kyoto, Japan Abstract: Immunoglobulin (Ig A nephropathy (IgAN is the most common form of glomerular disease worldwide and is associated with a poor prognosis. Thus, development of a curative treatment and strategies for early diagnosis and treatment are urgently needed. Pathological analysis of renal biopsy is the gold standard for the diagnosis and assessment of disease activity; however, immediate and frequent assessment based on biopsy specimens is difficult. Therefore, a simple and safe alternative is desirable. On the other hand, it is now widely accepted that multi-hit steps, including production of aberrantly glycosylated serum IgA1 (first hit, and IgG or IgA autoantibodies that recognize glycan containing epitopes on glycosylated serum IgA1 (second hit and their subsequent immune complex formation (third hit and glomerular deposition (fourth hit, are required for continued progression of IgAN. Although the prognostic and predictive values of several markers have been discussed elsewhere, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of glycosylated serum IgA1 and related IgA immune complex. In addition, we confirmed a significant correlation between serum levels of these essential effector molecules and disease activity after treatment, suggesting that each can be considered as a practical surrogate marker of therapeutic effects in this slowly progressive disease. Such a noninvasive diagnostic and activity assessment method using these disease-oriented specific biomarkers may be useful in the early diagnosis of and intervention in IgAN, with

  1. N-glycosylation in sugarcane

    Directory of Open Access Journals (Sweden)

    Maia Ivan G.

    2001-01-01

    Full Text Available The N-linked glycosylation of secretory and membrane proteins is the most complex posttranslational modification known to occur in eukaryotic cells. It has been shown to play critical roles in modulating protein function. Although this important biological process has been extensively studied in mammals, much less is known about this biosynthetic pathway in plants. The enzymes involved in plant N-glycan biosynthesis and processing are still not well defined and the mechanism of their genetic regulation is almost completely unknown. In this paper we describe our first attempt to understand the N-linked glycosylation mechanism in a plant species by using the data generated by the Sugarcane Expressed Sequence Tag (SUCEST project. The SUCEST database was mined for sugarcane gene products potentially involved in the N-glycosylation pathway. This approach has led to the identification and functional assignment of 90 expressed sequence tag (EST clusters sharing significant sequence similarity with the enzymes involved in N-glycan biosynthesis and processing. The ESTs identified were also analyzed to establish their relative abundance.

  2. Molecular partners of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, suggest its involvement in distinct cellular processes relevant to congenital disorders of glycosylation, cancer, neurodegeneration and a variety of further pathologies.

    Science.gov (United States)

    Hacker, Benedikt; Schultheiß, Christoph; Döring, Michael; Kurzik-Dumke, Ursula

    2018-06-01

    This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila Neighbour of TID and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1. We disclose the building of hNOT/ALG3 homodimers and provide experimental evidence for its in vivo interaction with the functionally linked proteins OSBP, OSBPL9 and LRP1, the SYPL1 protein and the transcription factor CREB3. Regarding the latter, we show that the 55 kDa N-glycosylated hNOT-1/ALG3-1 molecule binds the N-glycosylated CREB3 precursor but does not interact with CREB3's proteolytic products specific to the endoplasmic reticulum and to the nucleus. The interaction between the two partners is a prerequisite for the proteolytic activation of CREB3. In case of the further binding partners, our data suggest that hNOT-1/ALG3-1 interacts with both OSBPs and with their direct targets LRP1 and VAMP/VAP-A. Moreover, our results show that various partners of hNOT-1/ALG3-1 interact with its diverse post translationally processed products destined to distinct cellular compartments. Generally, our data suggest the involvement of hNOT-1/ALG3-1 in various molecular contexts determining essential processes associated with distinct cellular machineries and related to various pathologies, such as cancer, viral infections, neuronal and immunological disorders and CDG.

  3. Initiation of GalNAc-type O-glycosylation in the endoplasmic reticulum promotes cancer cell invasiveness

    DEFF Research Database (Denmark)

    Gill, David J; Tham, Keit Min; Chia, Joanne

    2013-01-01

    Invasiveness underlies cancer aggressiveness and is a hallmark of malignancy. Most malignant tumors have elevated levels of Tn, an O-GalNAc glycan. Mechanisms underlying Tn up-regulation and its effects remain unclear. Here we show that Golgi-to-endoplasmic reticulum relocation of polypeptide N-a...

  4. Biochemical characterization of individual human glycosylated pro-insulin-like growth factor (IGF)-II and big-IGF-II isoforms associated with cancer.

    Science.gov (United States)

    Greenall, Sameer A; Bentley, John D; Pearce, Lesley A; Scoble, Judith A; Sparrow, Lindsay G; Bartone, Nicola A; Xiao, Xiaowen; Baxter, Robert C; Cosgrove, Leah J; Adams, Timothy E

    2013-01-04

    Insulin-like growth factor II (IGF-II) is a major embryonic growth factor belonging to the insulin-like growth factor family, which includes insulin and IGF-I. Its expression in humans is tightly controlled by maternal imprinting, a genetic restraint that is lost in many cancers, resulting in up-regulation of both mature IGF-II mRNA and protein expression. Additionally, increased expression of several longer isoforms of IGF-II, termed "pro" and "big" IGF-II, has been observed. To date, it is ambiguous as to what role these IGF-II isoforms have in initiating and sustaining tumorigenesis and whether they are bioavailable. We have expressed each individual IGF-II isoform in their proper O-glycosylated format and established that all bind to the IGF-I receptor and both insulin receptors A and B, resulting in their activation and subsequent stimulation of fibroblast proliferation. We also confirmed that all isoforms are able to be sequestered into binary complexes with several IGF-binding proteins (IGFBP-2, IGFBP-3, and IGFBP-5). In contrast to this, ternary complex formation with IGFBP-3 or IGFBP-5 and the auxillary protein, acid labile subunit, was severely diminished. Furthermore, big-IGF-II isoforms bound much more weakly to purified ectodomain of the natural IGF-II scavenging receptor, IGF-IIR. IGF-II isoforms thus possess unique biological properties that may enable them to escape normal sequestration avenues and remain bioavailable in vivo to sustain oncogenic signaling.

  5. Biochemical Characterization of Individual Human Glycosylated pro-Insulin-like Growth Factor (IGF)-II and big-IGF-II Isoforms Associated with Cancer

    Science.gov (United States)

    Greenall, Sameer A.; Bentley, John D.; Pearce, Lesley A.; Scoble, Judith A.; Sparrow, Lindsay G.; Bartone, Nicola A.; Xiao, Xiaowen; Baxter, Robert C.; Cosgrove, Leah J.; Adams, Timothy E.

    2013-01-01

    Insulin-like growth factor II (IGF-II) is a major embryonic growth factor belonging to the insulin-like growth factor family, which includes insulin and IGF-I. Its expression in humans is tightly controlled by maternal imprinting, a genetic restraint that is lost in many cancers, resulting in up-regulation of both mature IGF-II mRNA and protein expression. Additionally, increased expression of several longer isoforms of IGF-II, termed “pro” and “big” IGF-II, has been observed. To date, it is ambiguous as to what role these IGF-II isoforms have in initiating and sustaining tumorigenesis and whether they are bioavailable. We have expressed each individual IGF-II isoform in their proper O-glycosylated format and established that all bind to the IGF-I receptor and both insulin receptors A and B, resulting in their activation and subsequent stimulation of fibroblast proliferation. We also confirmed that all isoforms are able to be sequestered into binary complexes with several IGF-binding proteins (IGFBP-2, IGFBP-3, and IGFBP-5). In contrast to this, ternary complex formation with IGFBP-3 or IGFBP-5 and the auxillary protein, acid labile subunit, was severely diminished. Furthermore, big-IGF-II isoforms bound much more weakly to purified ectodomain of the natural IGF-II scavenging receptor, IGF-IIR. IGF-II isoforms thus possess unique biological properties that may enable them to escape normal sequestration avenues and remain bioavailable in vivo to sustain oncogenic signaling. PMID:23166326

  6. Chemokines in cancer related inflammation

    Energy Technology Data Exchange (ETDEWEB)

    Allavena, Paola; Germano, Giovanni; Marchesi, Federica [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089, Rozzano, Milan (Italy); Mantovani, Alberto, E-mail: alberto.mantovani@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089, Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan (Italy)

    2011-03-10

    Chemokines are key players of the cancer-related inflammation. Chemokine ligands and receptors are downstream of genetic events that cause neoplastic transformation and are abundantly expressed in chronic inflammatory conditions which predispose to cancer. Components of the chemokine system affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis. Evidence in pre-clinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies.

  7. Cancer survivors. Work related issues.

    Science.gov (United States)

    Schultz, Pamela N; Beck, Martha L; Stava, Charles; Sellin, Rena V

    2002-05-01

    New and more effective treatments for cancer have resulted in individuals living longer with a better quality of life. Many more survivors are employed in the workplace. Cancer is no longer only an issue for survivors and their families; it has become an issue for the employer and the workplace. This article describes survey results of 4,364 long term cancer survivors in which they were asked to respond to items describing their ability to work, job discrimination, and quality of life. Thirty-five percent of survivors were working at the time they completed the survey, and 8.5% considered themselves unable to work. This research has shown that age, gender, ethnic group, and cancer type affected the working status of the survivors. Of survivors continuing to work, 7.3% indicated they had experienced job discrimination. The results indicate most cancer survivors do not perceive employment related problems, and are readily assimilated into the work force. Job discrimination and the ability to work is a quality of life issue.

  8. DISAL glycosyl donors for the synthesis of a linear hexasaccharide under mild conditions

    DEFF Research Database (Denmark)

    Petersen, Lars; Laursen, Jane B.; Larsen, K.

    2003-01-01

    The new class of glycosyl donors with a methyl 3,5-dinitrosalicylate (DISAL) anomeric leaving group has proved efficient for glycosylation under strictly neutral, mildly basic, or mildly acidic conditions. Here, we report the synthesis of novel DISAL disaccharide glycosyl donors prepared by easy...... nucleophilic aromatic substitution. These DISAL donors proved efficient in the synthesis of a starch-related hexasaccharide under very mild conditions. Glycosylations proceeded with alpha-selectivity and were compatible with Trt protecting groups....

  9. GLYCOSYLATED YGHJ POLYPEPTIDES FROM ENTEROTOXIGENIC ESCHERICHIA COLI (ETEC)

    DEFF Research Database (Denmark)

    2017-01-01

    The present invention relates to glycosylated YghJ polypeptides from or derived from enterotoxigenic Escherichia coli (ETEC) that are immunogenic. In particular, the present invention relates to compositions or vaccines comprising the polypeptides and their application in immunization, vaccination...

  10. Importance of N-Glycosylation on CD147 for Its Biological Functions

    Science.gov (United States)

    Bai, Yang; Huang, Wan; Ma, Li-Tian; Jiang, Jian-Li; Chen, Zhi-Nan

    2014-01-01

    Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation. PMID:24739808

  11. Importance of N-Glycosylation on CD147 for Its Biological Functions

    Directory of Open Access Journals (Sweden)

    Yang Bai

    2014-04-01

    Full Text Available Glycosylation of glycoproteins is one of many molecular changes that accompany malignant transformation. Post-translational modifications of proteins are closely associated with the adhesion, invasion, and metastasis of tumor cells. CD147, a tumor-associated antigen that is highly expressed on the cell surface of various tumors, is a potential target for cancer diagnosis and therapy. A significant biochemical property of CD147 is its high level of glycosylation. Studies on the structure and function of CD147 glycosylation provide valuable clues to the development of targeted therapies for cancer. Here, we review current understanding of the glycosylation characteristics of CD147 and the glycosyltransferases involved in the biosynthesis of CD147 N-glycans. Finally, we discuss proteins regulating CD147 glycosylation and the biological functions of CD147 glycosylation.

  12. GlycA, a marker of protein glycosylation, is related to albuminuria and estimated glomerular filtration rate: the ELSA-Brasil study.

    Science.gov (United States)

    Titan, Silvia M; Pecoits-Filho, Roberto; Barreto, Sandhi M; Lopes, Antônio Alberto; Bensenor, Isabela J; Lotufo, Paulo A

    2017-12-20

    Systemic inflammation has been implicated in several chronic diseases. GlycA is a new nuclear mass resonance (NMR) spectroscopy-derived biomarker of systemic inflammation that reflects protein glycosylation. We evaluated the association of GlycA with albuminuria and eGFR in the ELSA-Brasil Study. The cross-sectional association between GlycA (automated NMR LipoProfile(®) test spectra, LabCorp, Raleigh, NC), and overnight 12 h-albuminuria and CKD-EPI eGFR was evaluated among 5050 participants. GlycA was higher among older, women, smokers, alcohol abstemious, obese and in those with diabetes, hypertension or dyslipidemia. In addition, both eGFR and albuminuria were associated to GlycA. In linear regression, GlycA was independently associated with log albuminuria (B 0.03; 95%CI 0.02-0.04, P < 0.0001, per 1sd increase) and inversely related to eGFR (B -0.53; 95%CI -0.99 - -0.07, P < 0.02), even after adjustments including hsCRP. In logistic regression, GlycA was independently related to the risk of A2 or A3 albuminuria (OR 1.42, 95%CI 1.27-1.57, p < 0.0001, per 1sd increase), of having an eGFR < 60 ml/min/1.73m 2 (OR 1.26, 95%CI 1.12-1.41, p = 0.0003, per 1 sd) or of a combined diagnosis of both conditions (OR 1.35, 95%CI 1.23-1.46, p < 0.0001, per 1 sd). In the ROC curve, GlycA had a higher AUC in comparison to hsCRP (AUC 0.67 vs. 0.62, p = 0.06) for the association with albuminuria A2 or A3. The present study demonstrates that GlycA is associated with albuminuria and eGFR, independently of major risk factors for CKD progression, including (and with a stronger association than) hsCRP. GlycA should be further evaluated in CKD progression.

  13. Digestibility and IgE-Binding of Glycosylated Codfish Parvalbumin

    Science.gov (United States)

    de Jongh, Harmen H. J.; Robles, Carlos López; Nordlee, Julie A.; Lee, Poi-Wah; Baumert, Joseph L.; Hamilton, Robert G.; Taylor, Steve L.; Koppelman, Stef J.

    2013-01-01

    Food-processing conditions may alter the allergenicity of food proteins by different means. In this study, the effect of the glycosylation as a result of thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is investigated. Native and glycosylated parvalbumins were digested with pepsin at various conditions relevant for the gastrointestinal tract. Intact proteins and peptides were analysed for apparent molecular weight and IgE-binding. Glycosylation did not substantially affect the digestion. Although the peptides resulting from digestion were relatively large (3 and 4 kDa), the IgE-binding was strongly diminished. However, the glycosylated parvalbumin had a strong propensity to form dimers and tetramers, and these multimers bound IgE intensely, suggesting stronger IgE-binding than monomeric parvalbumin. We conclude that glycosylation of codfish parvalbumin does not affect the digestibility of parvalbumin and that the peptides resulting from this digestion show low IgE-binding, regardless of glycosylation. Glycosylation of parvalbumin leads to the formation of higher order structures that are more potent IgE binders than native, monomeric parvalbumin. Therefore, food-processing conditions applied to fish allergen can potentially lead to increased allergenicity, even while the protein's digestibility is not affected by such processing. PMID:23878817

  14. Digestibility and IgE-Binding of Glycosylated Codfish Parvalbumin

    Directory of Open Access Journals (Sweden)

    Harmen H. J. de Jongh

    2013-01-01

    Full Text Available Food-processing conditions may alter the allergenicity of food proteins by different means. In this study, the effect of the glycosylation as a result of thermal treatment on the digestibility and IgE-binding of codfish parvalbumin is investigated. Native and glycosylated parvalbumins were digested with pepsin at various conditions relevant for the gastrointestinal tract. Intact proteins and peptides were analysed for apparent molecular weight and IgE-binding. Glycosylation did not substantially affect the digestion. Although the peptides resulting from digestion were relatively large (3 and 4 kDa, the IgE-binding was strongly diminished. However, the glycosylated parvalbumin had a strong propensity to form dimers and tetramers, and these multimers bound IgE intensely, suggesting stronger IgE-binding than monomeric parvalbumin. We conclude that glycosylation of codfish parvalbumin does not affect the digestibility of parvalbumin and that the peptides resulting from this digestion show low IgE-binding, regardless of glycosylation. Glycosylation of parvalbumin leads to the formation of higher order structures that are more potent IgE binders than native, monomeric parvalbumin. Therefore, food-processing conditions applied to fish allergen can potentially lead to increased allergenicity, even while the protein’s digestibility is not affected by such processing.

  15. Cancer Risks for Relatives of Children with Cancer

    International Nuclear Information System (INIS)

    Heath, J. A.; Smibert, E.; Algar, E. M.; Heath, J. A.; Dite, G. S.; Hopper, J. L.; Algar, E. M.

    2014-01-01

    We determined the extent and distribution of cancers in relatives of 379 children newly diagnosed with cancer. Family history was collected from 1,337 first-degree and 3,399 second-degree relatives and incidence compared with national age- and gender-specific rates. Overall, 14 children (3.7%) had a relative with a history of childhood cancer and 26 children (6.9%) had a first-degree relative with a history of cancer, with only one of these having an identifiable familial cancer syndrome. There was a higher than expected incidence of childhood cancer among first-degree relatives (parents and siblings) (standardized incidence ratio (SIR) 1.43; 95% CI 0.54-5.08). There was also a higher than expected incidence of adult cancers among first-degree relatives (SIR 1.45; 95% CI 0.93-2.21), particularly in females (SIR 1.82; 95% CI 1.26-3.39). The increased family cancer history in first-degree females was largely attributable to an effect in mothers (SIR 1.78; 95% CI 1.27-3.33). The gender-specific association was reflected in higher than expected incidence rates of breast cancer in both mothers (SIR 1.92; 95% CI 0.72-6.83) and aunts (SIR 1.64; 95% CI 0.98-2.94). These findings support the hypothesis that previously undetected familial cancer syndromes contribute to childhood cancer.

  16. Biochemical Importance of Glycosylation of Plasminogen Activator Inhibitor-1

    DEFF Research Database (Denmark)

    Gils, Ann; Pedersen, Katrine Egelund; Skottrup, Peter Durand

    2003-01-01

    The serpin plasminogen activator inhibitor-1 (PAI-1) is a potential target for anti-thrombotic and anti-cancer therapy. PAI-1 has 3 potential sites for N-linked glycosylation. We demonstrate here that PAI-1 expressed recombinantly or naturally by human cell lines display a heterogeneous glycosyla...

  17. Nonenzymatic glycosylation of bovine myelin basic protein

    International Nuclear Information System (INIS)

    Hitz, J.B.

    1987-01-01

    In the CNS myelin sheath the nonenzymatic glycosylation reaction (at the early stage of the Amadori product) occurs only with the myelin basic protein and not with the other myelin proteins. This was observed in isolated bovine myelin by in vitro incubation with [ 14 C]-galactose and [ 14 C]-glucose. The respective in-vitro incorporation rates for purified bovine myelin basic protein with D-galactose, D-glucose and D-mannose were 7.2, 2.4 and 2.4 mmoles/mole myelin basic protein per day at 37 0 C. A more rapid, HPLC method was devised and characterized to specifically analyze for the Amadori product. The HPLC method was correlated to the [ 14 C]-sugar incorporation method for myelin basic protein under a set of standard reaction conditions using [ 14 C]-glucose and [ 14 C]-mannose with HPLC values at 1/6 and 1/5 of the [ 14 C]-sugar incorporation method. A novel myelin basic protein purification step has been developed that yields a relativity proteolytic free preparation that is easy to work with, being totally soluble at a neutral pH. Nine new spots appear for a trypsinized glycosylated MBP in the paper peptide map of which eight correspond to positions of the [ 3 H]-labeled Amadori product in affinity isolated peptides. These studies provide a general characterization of and a structural basis for investigations on nonenzymatically glycosylated MBP as well as identifying MBP as the only nonenzymatically glycosylated protein in the CNS myelin sheath which may accumulate during aging, diabetes, and demyelinating diseases in general

  18. Diversity in protein glycosylation among insect species.

    Directory of Open Access Journals (Sweden)

    Gianni Vandenborre

    Full Text Available BACKGROUND: A very common protein modification in multicellular organisms is protein glycosylation or the addition of carbohydrate structures to the peptide backbone. Although the Class of the Insecta is the largest animal taxon on Earth, almost all information concerning glycosylation in insects is derived from studies with only one species, namely the fruit fly Drosophila melanogaster. METHODOLOGY/PRINCIPAL FINDINGS: In this report, the differences in glycoproteomes between insects belonging to several economically important insect orders were studied. Using GNA (Galanthus nivalis agglutinin affinity chromatography, different sets of glycoproteins with mannosyl-containing glycan structures were purified from the flour beetle (Tribolium castaneum, the silkworm (Bombyx mori, the honeybee (Apis mellifera, the fruit fly (D. melanogaster and the pea aphid (Acyrthosiphon pisum. To identify and characterize the purified glycoproteins, LC-MS/MS analysis was performed. For all insect species, it was demonstrated that glycoproteins were related to a broad range of biological processes and molecular functions. Moreover, the majority of glycoproteins retained on the GNA column were unique to one particular insect species and only a few glycoproteins were present in the five different glycoprotein sets. Furthermore, these data support the hypothesis that insect glycoproteins can be decorated with mannosylated O-glycans. CONCLUSIONS/SIGNIFICANCE: The results presented here demonstrate that oligomannose N-glycosylation events are highly specific depending on the insect species. In addition, we also demonstrated that protein O-mannosylation in insect species may occur more frequently than currently believed.

  19. Other cancers in lung cancer families are overwhelmingly smoking-related cancers

    Directory of Open Access Journals (Sweden)

    Hongyao Yu

    2017-06-01

    Full Text Available Familial risks of lung cancer are well-established, but whether lung cancer clusters with other discordant cancers is less certain, particularly beyond smoking-related sites, which may provide evidence on genetic contributions to lung cancer aetiology. We used a novel approach to search for familial associations in the Swedish Family-Cancer Database. This involved assessment of familial relative risk for cancer X in families with increasing numbers of lung cancer patients and, conversely, relative risks for lung cancer in families with increasing numbers of patients with cancers X. However, we lacked information on smoking. The total number of lung cancers in the database was 125 563. We applied stringent statistical criteria and found that seven discordant cancers were associated with lung cancer among family members, and six of these were known to be connected with smoking: oesophageal, upper aerodigestive tract, liver, cervical, kidney and urinary bladder cancers. A further novel finding was that cancer of unknown primary also associated with lung cancer. We also factored in histological evidence and found that anal and connective tissue cancers could be associated with lung cancer for reasons other than smoking. For endometrial and prostate cancers, suggestive negative associations with lung cancer were found. Although we lacked information on smoking it is prudent to conclude that practically all observed discordant associations of lung cancer were with cancers for which smoking is a risk factor.

  20. Diversity and functions of protein glycosylation in insects.

    Science.gov (United States)

    Walski, Tomasz; De Schutter, Kristof; Van Damme, Els J M; Smagghe, Guy

    2017-04-01

    The majority of proteins is modified with carbohydrate structures. This modification, called glycosylation, was shown to be crucial for protein folding, stability and subcellular location, as well as protein-protein interactions, recognition and signaling. Protein glycosylation is involved in multiple physiological processes, including embryonic development, growth, circadian rhythms, cell attachment as well as maintenance of organ structure, immunity and fertility. Although the general principles of glycosylation are similar among eukaryotic organisms, insects synthesize a distinct repertoire of glycan structures compared to plants and vertebrates. Consequently, a number of unique insect glycans mediate functions specific to this class of invertebrates. For instance, the core α1,3-fucosylation of N-glycans is absent in vertebrates, while in insects this modification is crucial for the development of wings and the nervous system. At present, most of the data on insect glycobiology comes from research in Drosophila. Yet, progressively more information on the glycan structures and the importance of glycosylation in other insects like beetles, caterpillars, aphids and bees is becoming available. This review gives a summary of the current knowledge and recent progress related to glycan diversity and function(s) of protein glycosylation in insects. We focus on N- and O-glycosylation, their synthesis, physiological role(s), as well as the molecular and biochemical basis of these processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Functional importance of PAI-1 glycosylation

    DEFF Research Database (Denmark)

    Christensen, Anni; Naessens, Dominik; Skottrup, Peter

    2001-01-01

    Structure-function studies of plasminogen activator inhibitor-1 (PAI-1) have previously been performed mostly with non-glycosylated material expressed in E. coli. We have now studied the importance of PAI-1 glycosylation for its functional properties. PAI-1 has 3 potential sites for N......-glycosylated PAI-1 could be conferred upon PAI-1 expressed in HEK293 cells by mutational inactivation of one or the other glycosylation site. These findings reveal a novel functional role for glycosylation of a serpin. The glycosylation sites are localised between a-helix H and b-strand 2C and b-strand 3C and a...

  2. Mortality in Individuals Aged 80 and Older with Type 2 Diabetes Mellitus in Relation to Glycosylated Hemoglobin, Blood Pressure, and Total Cholesterol.

    Science.gov (United States)

    Hamada, Shota; Gulliford, Martin C

    2016-07-01

    To evaluate whether low glycosylated hemoglobin (HbA1c), blood pressure (BP), and total cholesterol (TC) are associated with lower risk of all-cause mortality in very old individuals with type 2 diabetes mellitus. Population-based cohort study. Primary care database in the United Kingdom. Individuals aged 80 and older with type 2 diabetes mellitus (N = 25,966). Associations between baseline HbA1c, BP, and TC and all-cause mortality were evaluated in Cox proportional hazards models. Analyses were adjusted for sex, age, duration of diabetes mellitus, lifestyle variables, HbA1c, BP, TC, comorbidities, prescribing of antidiabetic and cardiovascular drugs, and participants' general practice. There were 4,490 deaths during follow-up (median 2.0 years; mortality 104.7 per 1,000 person-years). Mortality in participants with low (type 2 diabetes mellitus. Further research is required to understand these associations and to identify optimal treatment targets in this population. © 2016 The Authors. The Journal of the American Geriatrics Society published by Wiley Periodicals, Inc. on behalf of The American Geriatrics Society.

  3. Enzymatic glycosylation of multivalent scaffolds

    Czech Academy of Sciences Publication Activity Database

    Bojarová, Pavla; Rosencrantz, R. R.; Elling, L.; Křen, Vladimír

    2013-01-01

    Roč. 42, č. 11 (2013), s. 4774-4797 ISSN 0306-0012 R&D Projects: GA MŠk(CZ) LD13042; GA ČR GAP207/10/0321 Institutional support: RVO:61388971 Keywords : N-ACETYLGLUCOSAMINYLTRANSFERASE-III * MUCIN TANDEM REPEAT * NEIGHBORING RESIDUE GLYCOSYLATION Subject RIV: CC - Organic Chemistry Impact factor: 30.425, year: 2013

  4. Radiation related basic cancer research

    International Nuclear Information System (INIS)

    Lee, Seung Hoon; Yoo, Young Do; Hong, Seok Il

    2000-04-01

    We studied the mechanism of radiation-induced apoptosis, the factors involved signaling, and the establishment of radiation-resistant cell lines in this study. During the TGF beta-stimulated epithelial mesenchymal transition(EMT), actin rearrangement occurred first and fibronectin matrix assembly followed. These two events were considered independent since cytochalasin-D did not inhibit TGF stimulated matrix assembly and fibronectin supplementation did not induce EMT. During EMT, alpha 5 beta 1 integrin and alpha v integrin have increased but MMP activation was not accompanied, which suggest that induction of extracellular matrix and activation of integrins may be main contributor for the EMT. Serum depriving induced apoptosis of HUVECs was prevented by vascular endothelial growth factor(VEGF) and PMA. The apoptosis prevention by VEGF and PMA were conformed by DNA fragmentation assay. The p53 expression level was down regulated by VEGF and PMA compared with serum deprived HUVECs. However, VEGF and PMA induces c-Myc expression level on these cells. We made the 5 radiation-resistant clones from breast, lung and cervical cancer cells. More than 70%, 100% and 50% increased resistance was detected in breast cancer cells, lung cancer cells, and cervical cells, respectively. We carried out differential display-PCR to clone the radiation-resistant genes. 9 out of 10 genes were analyzed their sequence

  5. Radiation related basic cancer research

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Hoon; Yoo, Young Do; Hong, Seok Il [and others

    2000-04-01

    We studied the mechanism of radiation-induced apoptosis, the factors involved signaling, and the establishment of radiation-resistant cell lines in this study. During the TGF beta-stimulated epithelial mesenchymal transition(EMT), actin rearrangement occurred first and fibronectin matrix assembly followed. These two events were considered independent since cytochalasin-D did not inhibit TGF stimulated matrix assembly and fibronectin supplementation did not induce EMT. During EMT, alpha 5 beta 1 integrin and alpha v integrin have increased but MMP activation was not accompanied, which suggest that induction of extracellular matrix and activation of integrins may be main contributor for the EMT. Serum depriving induced apoptosis of HUVECs was prevented by vascular endothelial growth factor(VEGF) and PMA. The apoptosis prevention by VEGF and PMA were conformed by DNA fragmentation assay. The p53 expression level was down regulated by VEGF and PMA compared with serum deprived HUVECs. However, VEGF and PMA induces c-Myc expression level on these cells. We made the 5 radiation-resistant clones from breast, lung and cervical cancer cells. More than 70%, 100% and 50% increased resistance was detected in breast cancer cells, lung cancer cells, and cervical cells, respectively. We carried out differential display-PCR to clone the radiation-resistant genes. 9 out of 10 genes were analyzed their sequence.

  6. Prion propagation in cells expressing PrP glycosylation mutants.

    Science.gov (United States)

    Salamat, Muhammad K; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

    2011-04-01

    Infection by prions involves conversion of a host-encoded cell surface protein (PrP(C)) to a disease-related isoform (PrP(Sc)). PrP(C) carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrP(C) glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrP(Sc) and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrP(Sc), while PrP(C) with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrP(C), were able to form infectious PrP(Sc). Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection.

  7. [Cancer-vitamins-minerals: Complex relation].

    Science.gov (United States)

    Adrianza de Baptista, Gertrudis; Murillo Melo, Carolain

    2014-12-01

    Since nutrition can influence the process of carcinogenesis, this study's objectives are to review the relationship between nutrition and cancer from the point of view of the role of micronutrients in the treatment of cancer patients, and to get to know the deficit relationship and the excess of micronutrients, with the etiology and cancer treatment. At the same time the patient's weight loss relates, among other things, to the type of cancerous tumor, its location, stage thereof, reason for which it may be associated with the deficiency of macro and micronutrients as from psychogenic, anorectics and mal-absorption effects or with mechanical effects as obstruction, among other toxic effects that are common in the treatment of cancer. Hence, the importance that the nutrition expert must have in making an adequate overall nutritional evaluation that allows the nutritional diagnosis, in studying the dietary patterns, to determine the toxic effects of the antineoplastic treatment in order to handle the treatment's timing excellence, symptoms and signs, and thus act effectively optiimizing the patient's life quality, and therewith his/her survival. There are controversies as to which specific dietary factors are related to cancer etiology and the results of studies on metabolic factors, and therefore, the relationship Cancer-Nutrition is quiet complex.

  8. Urological cancer related to familial syndromes

    Directory of Open Access Journals (Sweden)

    Walter Henriques da Costa

    Full Text Available ABSTRACT Cancer related to hereditary syndromes corresponds to approximately 5-10% of all tumors. Among those from the genitourinary system, many tumors had been identified to be related to genetic syndromes in the last years with the advent of new molecular genetic tests. New entities were described or better characterized, especially in kidney cancer such as hereditary leiomyomatosis renal cell carcinoma (HLRCC, succinate dehydrogenase kidney cancer (SDH-RCC, and more recently BAP1 germline mutation related RCC. Among tumors from the bladder or renal pelvis, some studies had reinforced the role of germline mutations in mismatch repair (MMR genes, especially in young patients. In prostate adenocarcinoma, besides mutations in BRCA1 and BRCA2 genes that are known to increase the incidence of high-risk cancer in young patients, new studies have shown mutation in other gene such as HOXB13 and also polymorphisms in MYC, MSMB, KLK2 and KLK3 that can be related to hereditary prostate cancer. Finally, tumors from testis that showed an increased in 8 - 10-fold in siblings and 4 - 6-fold in sons of germ cell tumors (TGCT patients, have been related to alteration in X chromosome. Also genome wide association studies GWAS pointed new genes that can also be related to increase of this susceptibility.

  9. Glycosylation Disorders with Immunodeficiency

    Science.gov (United States)

    ... Relations Cyber Infrastructure Computational Biology Equal Employment Opportunity Ethics Global Research Office of Mission Integration and Financial Management Strategic Planning Workforce Effectiveness Workplace Solutions Technology Transfer Intellectual Property Division of AIDS ...

  10. Aberrantly glycosylated MUC1 is expressed on the surface of breast cancer cells and a target for antibody-dependent cell-mediated cytotoxicity

    DEFF Research Database (Denmark)

    Lavrsen, Kirstine; Madsen, Caroline B; Rasch, Morten G

    2013-01-01

    to Tn-MUC1 was investigated using BiaCore. The availability of Tn-MUC1 on the surface of breast cancer cells was evaluated by immunohistochemistry, confocal microscopy, and flow cytometry, followed by in vitro assessment of antibody-dependent cellular cytotoxicity by mAb 5E5. Biacore analysis...

  11. Dendritic cells recognize tumor-specific glycosylation of carcinoembryonic antigen on colorectal cancer cells through dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin

    NARCIS (Netherlands)

    van Gisbergen, Klaas P. J. M.; Aarnoudse, Corlien A.; Meijer, Gerrit A.; Geijtenbeek, Teunis B. H.; van Kooyk, Yvette

    2005-01-01

    Dendritic cells play a pivotal role in the induction of antitumor immune responses. Immature dendritic cells are located intratumorally within colorectal cancer and intimately interact with tumor cells, whereas mature dendritic cells are present peripheral to the tumor. The majority of colorectal

  12. Unusual glycosylation of proteins: Beyond the universal sequon and other amino acids.

    Science.gov (United States)

    Dutta, Devawati; Mandal, Chhabinath; Mandal, Chitra

    2017-12-01

    Glycosylation of proteins is the most common, multifaceted co- and post-translational modification responsible for many biological processes and cellular functions. Significant alterations and aberrations of these processes are related to various pathological conditions, and often turn out to be disease biomarkers. Conventional N-glycosylation occurs through the recognition of the consensus sequon, asparagine (Asn)-X-serine (Ser)/threonine (Thr), where X is any amino acid except for proline, with N-acetylglucosamine (GlcNAc) as the first glycosidic linkage. Usually, O-glycosylation adds a glycan to the hydroxyl group of Ser or Thr beginning with N-acetylgalactosamine (GalNAc). Protein glycosylation is further governed by additional diversifications in sequon and structure, which are yet to be fully explored. This review mainly focuses on the occurrence of N-glycosylation in non-consensus motifs, where Ser/Thr at the +2 position is substituted by other amino acids. Additionally, N-glycosylation is also observed in other amide/amine group-containing amino acids. Similarly, O-glycosylation occurs at hydroxyl group-containing amino acids other than serine/threonine. The neighbouring amino acids and local structural features around the potential glycosylation site also play a significant role in determining the extent of glycosylation. All of these phenomena that yield glycosylation at the atypical sites are reported in a variety of biological systems, including different pathological conditions. Therefore, the discovery of more novel sequence patterns for N- and O-glycosylation may help in understanding the functions of complex biological processes and cellular functions. Taken together, all these information provided in this review would be helpful for the biological readers. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Glycosylation profiles of therapeutic antibody pharmaceuticals.

    Science.gov (United States)

    Wacker, Christoph; Berger, Christoph N; Girard, Philippe; Meier, Roger

    2011-11-01

    Recombinant antibodies specific for human targets are often used as therapeutics and represent a major class of drug products. Their therapeutic efficacy depends on the formation of antibody complexes resulting in the elimination of a target molecule or the modulation of specific signalling pathways. The physiological effects of antibody therapeutics are known to depend on the structural characteristics of the antibody molecule, specifically on the glycosylation which is the result of posttranslational modifications. Hence, production of therapeutic antibodies with a defined and consistent glycoform profile is needed which still remains a considerable challenge to the biopharmaceutical industry. To provide an insight into the industries capability to control their manufacturing process and to provide antibodies of highest quality, we conducted a market surveillance study and compared major oligosaccharide profiles of a number of monoclonal antibody pharmaceuticals sampled on the Swiss market. Product lot-to-lot variability was found to be generally low, suggesting that a majority of manufacturers have implemented high quality standards in their production processes. However, proportions of G0, G1 and G2 core-fucosylated chains derived from different products varied considerably and showed a bias towards the immature agalactosidated G0 form. Interestingly, differences in glycosylation caused by the production cell type seem to be of less importance compared with process related parameters such as cell growth. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Prediction of glycosylation sites using random forests

    Directory of Open Access Journals (Sweden)

    Hirst Jonathan D

    2008-11-01

    Full Text Available Abstract Background Post translational modifications (PTMs occur in the vast majority of proteins and are essential for function. Prediction of the sequence location of PTMs enhances the functional characterisation of proteins. Glycosylation is one type of PTM, and is implicated in protein folding, transport and function. Results We use the random forest algorithm and pairwise patterns to predict glycosylation sites. We identify pairwise patterns surrounding glycosylation sites and use an odds ratio to weight their propensity of association with modified residues. Our prediction program, GPP (glycosylation prediction program, predicts glycosylation sites with an accuracy of 90.8% for Ser sites, 92.0% for Thr sites and 92.8% for Asn sites. This is significantly better than current glycosylation predictors. We use the trepan algorithm to extract a set of comprehensible rules from GPP, which provide biological insight into all three major glycosylation types. Conclusion We have created an accurate predictor of glycosylation sites and used this to extract comprehensible rules about the glycosylation process. GPP is available online at http://comp.chem.nottingham.ac.uk/glyco/.

  15. Flagellar glycosylation in Clostridium botulinum.

    Science.gov (United States)

    Twine, Susan M; Paul, Catherine J; Vinogradov, Evgeny; McNally, David J; Brisson, Jean-Robert; Mullen, James A; McMullin, David R; Jarrell, Harold C; Austin, John W; Kelly, John F; Logan, Susan M

    2008-09-01

    Flagellins from Clostridium botulinum were shown to be post-translationally modified with novel glycan moieties by top-down MS analysis of purified flagellin protein from strains of various toxin serotypes. Detailed analyses of flagellin from two strains of C. botulinum demonstrated that the protein is modified by a novel glycan moiety of mass 417 Da in O-linkage. Bioinformatic analysis of available C. botulinum genomes identified a flagellar glycosylation island containing homologs of genes recently identified in Campylobacter coli that have been shown to be responsible for the biosynthesis of legionaminic acid derivatives. Structural characterization of the carbohydrate moiety was completed utilizing both MS and NMR spectroscopy, and it was shown to be a novel legionaminic acid derivative, 7-acetamido-5-(N-methyl-glutam-4-yl)-amino-3,5,7,9-tetradeoxy-D-glycero-alpha-D-galacto-nonulosonic acid, (alphaLeg5GluNMe7Ac). Electron transfer dissociation MS with and without collision-activated dissociation was utilized to map seven sites of O-linked glycosylation, eliminating the need for chemical derivatization of tryptic peptides prior to analysis. Marker ions for novel glycans, as well as a unique C-terminal flagellin peptide marker ion, were identified in a top-down analysis of the intact protein. These ions have the potential for use in for rapid detection and discrimination of C. botulinum cells, indicating botulinum neurotoxin contamination. This is the first report of glycosylation of Gram-positive flagellar proteins by the 'sialic acid-like' nonulosonate sugar, legionaminic acid.

  16. Distribution of N-glycosylation sequons in proteins: how apart are they?

    DEFF Research Database (Denmark)

    Rao, Shyama Prasad; Buus, Ole Thomsen; Wollenweber, Bernd

    2011-01-01

    of experimentally confirmed eukaryotic N-glycoproteins we analyzed the relative position and distribution of sequons. N-Glycosylation probability was found to be lower in the termini of protein sequences compared to the mid region. N-glycosylated sequons were found much farther from C terminus compared to the N......N-glycosylation is a common protein modification process, which affects a number of properties of proteins. Little is known about the distribution of N-glycosylation sequons, for example, the distance between glycosylated sites and their position in the protein primary sequence. Using a large set......-terminus of the protein sequence and this effect was more pronounced for NXS sequons. The distribution of sequons, modeled based on balls-in-boxes classical occupancy, showed a near-maximum probability. Considerable proportion of sequons was found within a distance of ten amino acids, indicating that the steric hindrance...

  17. Aids-Related Cancers in Africa

    Science.gov (United States)

    Mbulaiteye, Sam M.

    2014-07-01

    Thank you Professor Zichichi for inviting me to give a talk about AIDS-related cancers in Africa. Let me begin by congratulating the team that organized the 46th Session of the Erice International Seminar Series, whose theme is THE ROLE OF SCIENCE IN THE THIRD MILLENIUM. I also congratulate the scientists from 38 countries who are attending these seminars. They are perpetuating the principle of SCIENCE WITHOUT SECRETS in the true spirit espoused by Archimedes, Galileo, and Fermi. It is a wonderful honor for me to be here to shed some light on the health impacts of the HIV epidemic in the area of cancer...

  18. Involvement of Relatives in Cancer Rehabilitation

    DEFF Research Database (Denmark)

    Ledderer, Loni; Madsen, Biddy; Mogensen, Ole

    2010-01-01

    using validated questionnaires including EORTC QLQ-C30, POMS, WHO-5 well-being index and supplemented with ad hoc questions. The rehabilitation needs are furthermore explored in qualitative interviews and participant-observations with pairs from both the intervention and the control group. Result...... with lung cancer or gynecological cancer are included in the study together with a relative by patient’s choice both giving informed consent (N=120 pairs). The intervention group (60 pairs) receives three supportive conversations with a trained nurse initiated from the admission date and completed within...

  19. Stemness-related markers in cancer

    Directory of Open Access Journals (Sweden)

    Wenxiu Zhao

    2017-01-01

    Full Text Available Cancer stem cells (CSCs, with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive tumor initiation, growth, and resistance to therapy. Like embryonic and adult stem cells, CSCs express markers that are not expressed in normal somatic cells and are thus thought to contribute toward a “stemness” phenotype. This review summarizes the current knowledge of stemness-related markers in human cancers, with a particular focus on important transcription factors, protein surface markers, and signaling pathways.

  20. Cancer Communication on Social Media: Examining How Cancer Caregivers Use Facebook for Cancer-Related Communication.

    Science.gov (United States)

    Gage-Bouchard, Elizabeth A; LaValley, Susan; Mollica, Michelle; Beaupin, Lynda Kwon

    Americans are increasingly using social media (such as Facebook, YouTube, and Twitter) for health-related communication. Much of the previous research on social media and health communication has focused on Facebook groups related to a specific disease or Facebook pages related to an advocacy organization. Less is known about how people communicate about cancer on personal Facebook pages. In this study, we expand upon previous research by examining how cancer caregivers use personal Facebook pages for cancer-related communication. We examined themes in cancer-related exchanges through a content analysis of 12 months of data from 18 publically available Facebook pages hosted by parents of children with acute lymphoblastic leukemia (15 852 total posts). Six themes emerged: (1) documenting the cancer journey, (2) sharing emotional strain associated with caregiving, (3) promoting awareness and advocacy about pediatric cancer, (4) fundraising, (5) mobilizing support, and (6) expressing gratitude for support. Building upon previous research documenting the increasing use of social media for health-related communication and support, our findings show that personal Facebook pages offer a platform for cancer caregivers to share their cancer-related experiences, promote advocacy and awareness, and mobilize social support. Providers must recognize the importance of social media as a vehicle for support and communication for families of children with cancer. Nurses should educate parents on how to appraise information obtained through Facebook using evidence-based guidelines. Providers can encourage caregivers to use Facebook as a tool for communication, information, and support.

  1. Statin use and reduced cancer-related mortality

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Nordestgaard, Børge G; Bojesen, Stig E

    2012-01-01

    A reduction in the availability of cholesterol may limit the cellular proliferation required for cancer growth and metastasis. We tested the hypothesis that statin use begun before a cancer diagnosis is associated with reduced cancer-related mortality.......A reduction in the availability of cholesterol may limit the cellular proliferation required for cancer growth and metastasis. We tested the hypothesis that statin use begun before a cancer diagnosis is associated with reduced cancer-related mortality....

  2. Management of Dysgeusia related to Cancer

    Directory of Open Access Journals (Sweden)

    DURGESHWORI MUNANKARMI

    2017-05-01

    Full Text Available Introduction: Taste change due to cancer is a notorious side effect, adversely affecting appetite and weight. Even though taste change or dysgeusia is one of the major causes of poor nutritional status in cancer survivors, it is not addressed as a significant problem and is often left untreated. The main purpose of this review is to explore current knowledge of pharmacological and behavioral interventions for the treatment of cancer related taste change. Methods: This systematic review was conducted in accordance with PRISMA guidelines to identify original articles on taste change. Multiple databases including; Scopus, Medline, EMBASE, CINAHL, and all databases via Pro quest were searched for original articles or studies related to taste change caused by cancer or its treatment. Relevant articles were subjected to a full text evaluation and assessed by Critical appraisal skills program (CASP guidelines and the Effective public health practice project (EPHPP instrument. Results: The search revealed 12 eligible studies, six of which were randomized controlled trials. Most of the studies used a standardized validated tool to measure taste change. Dysgeusia is common in cancer, 14 to 100% cancer patient report it. Pharmacological management with zinc remains inconclusive as one study reports it as beneficial and two other studies reported null effect. Few studies suggested dietary modifications such as use of sugary, salty foods that are helpful to reduce the effect of dysgeusia. Conclusion: Dietary counseling and informing the patient well about self-care strategies before treatment has consistently shown positive results on taste change, with strong statistical power. Other potential treatments for dysgeusia such as zinc, amifostine, and megestrol acetate gave inconsistent results.

  3. Marked increase in rat red blood cell membrane protein glycosylation by one-month treatment with a cafeteria diet

    Directory of Open Access Journals (Sweden)

    Laia Oliva

    2015-07-01

    RBC were lower than those of plasma, even when expressed in molal units, and were practically nil in cafeteria-diet fed rats compared with controls; there was no effect of sex.Conclusions. RBC membrane glycosylation is a sensitive indicator of developing metabolic syndrome-related hyperglycemia, more sensitive than the general measurement of plasma or RBC protein glycosylation. The extensive glycosylation of blood proteins does not seem to be markedly affected by sex; and could be hardly justified from an assumedly sustained plasma hyperglycemia. The low levels of glucose found within RBC, especially in rats under the cafeteria diet, could hardly justify the extensive glycosylation of hemoglobin and the lack of differences with controls, which contained sizeable levels of intracellular glucose. Additional studies are needed to study the dynamics of glucose in vivo in the RBC to understand how such extensive protein glycosylation could take place.

  4. Functional importance of PAI-1 glycosylation

    DEFF Research Database (Denmark)

    Christensen, Anni; Naessens, Dominik; Skottrup, Peter

    susceptible PAI-1 variant was not necessarily the one used when raising the antibody. This and other observations indicated that the carbohydrate moieties or the glycosylation sites are unlikely to be part of the epitopes for these antibodies. The antibody susceptibility characteristic for non......Structure-function studies of plasminogen activator inhibitor-1 (PAI-1) have previously been performed mostly with non-glycosylated material expressed in E. coli. We have now studied the importance of PAI-1 glycosylation for its functional properties. PAI-1 has 3 potential sites for N......-linked glycosylation. Biochemical analysis of PAI-1 variants with substitutions of the Asn residues in each of these sites and expression in human embryonic kidney 293 (HEK293) cells showed that only Asn211 and Asn 267, but not Asn331 are glycosylated, and revealed a differential composition of the carbohydrate...

  5. Comparative Glycoproteome Analysis: Dynamics of Protein Glycosylation during Metamorphic Transition from Pelagic to Benthic Life Stages in Three Invertebrates

    KAUST Repository

    Chandramouli, Kondethimmanahalli

    2012-02-03

    The life cycle of most benthic marine invertebrates has two distinct stages: the pelagic larval stage and the sessile juvenile stage. The transition between the larval stage and the juvenile stage is often abrupt and may be triggered by post-translational modification of proteins. Glycosylation, a very important post-translational modification, influences the biological activity of proteins. We used two-dimensional gel electrophoresis (2-DE) followed by glycoprotein-specific fluorescence staining and mass spectrometry with the goal of identifying glycosylation pattern changes during larval settlement and metamorphosis in barnacles, bryozoans, and polychaetes. Our results revealed substantial changes in the protein glycosylation patterns from larval to juvenile stages. Before metamorphosis, the degree of protein glycosylation was high in the barnacle Balanus (=Amphibalanus) amphitrite and the spionid polychaete Pseudopolydora vexillosa, whereas it increased after metamorphosis in the bryozoan Bugula neritina. We identified 19 abundant and differentially glycosylated proteins in these three species. Among the proteins, cellular stress- and metabolism-related proteins exhibited distinct glycosylation in B. amphitrite and B. neritina, whereas fatty acid metabolism-related proteins were abundantly glycosylated in P. vexillosa. Furthermore, the protein and gene expression analysis of some selected glycoproteins revealed that the degree of protein glycosylation did not always complement with transcriptional and translational changes associated with the larval-juvenile transition. The current study provides preliminary information on protein glycosylation in marine invertebrates that will serve as a solid basis for future comprehensive analysis of glycobiology during larval settlement and metamorphosis. © 2011 American Chemical Society.

  6. Understanding Alzheimer's disease by global quantification of protein phosphorylation and sialylated N-linked glycosylation profiles

    DEFF Research Database (Denmark)

    Lassen, Pernille S.; Thygesen, Camilla; Larsen, Martin R.

    2017-01-01

    elucidated them in neurodegenerative diseases such as Alzheimer's disease. Here, we comprehensively review Alzheimer's pathology in relation to protein phosphorylation and glycosylation on synaptic plasticity from neuroproteomics data. Moreover, we highlight several mass spectrometry-based sample processing...

  7. Unmodifiable variables related to thyroid cancer incidence

    Directory of Open Access Journals (Sweden)

    Cornelia Nitipir

    2018-04-01

    Full Text Available The incidence of thyroid cancer is significantly different between male and female patients. Thyroid cancer is also the only form of cancer where age can be considered a staging variable. Identifying biological prognostic factors such as age or sex is important as it helps select an optimal personalized therapy. The present analysis is an observational, prospective study that enrolled all patients with thyroid disease who were operated upon at a single center. The study aimed to determine the most frequent age at presentation, the predominance of one sex over the other, the incidence of malignant thyroid disease, and the relative risk for each sex to develop thyroid carcinoma. The incidence of thyroid carcinoma was higher for women than for men, with a higher relative risk in the female subgroup. Incidence was also highest in the 50-60-year-old group. Given that studies show better survival for women and for younger patients, even when presenting with advanced disease, compared with older, male patients, such prognostic indicators should be a factor in the treatment decision.

  8. Pregnancy-related venous thromboembolism and risk of occult cancer

    DEFF Research Database (Denmark)

    Hansen, Anette Tarp; Veres, Katalin; Horváth-Puhó, Erzsébet

    2017-01-01

    The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected. An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk.......The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected. An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk....

  9. 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

    of expression of these antigens in the benign lesions was similar to that of normal oral mucosa, i.e. expression of: N-acetyllactosamine on basal cells, H antigen on parabasal cells, and Lex and Ley on spinous cells. However, lesions with epithelial dysplasia showed H antigen on all spinous cells, and often......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...... also on basal cells, with expression of Lex and Ley restricted to the most superficial part of the epithelium above the H-positive cell layers. In carcinomas most cells were negative for H antigen but were positive for Ley and Lex in 5 out of 8 cases....

  10. Multidimensional fractionation is a requirement for quantitation of Golgi-resident glycosylation enzymes from cultured human cells.

    Science.gov (United States)

    Lin, Chi-Hung; Chik, Jenny H L; Packer, Nicolle H; Molloy, Mark P

    2015-02-06

    Glycosylation results from the concerted action of glycosylation enzymes in the secretory pathway. In general, gene expression serves as the primary control mechanism, but post-translational fine-tuning of glycosylation enzyme functions is often necessary for efficient synthesis of specific glycan epitopes. While the field of glycomics has rapidly advanced, there lacks routine proteomic methods to measure expression of specific glycosylation enzymes needed to fill the gap between mRNA expression and the glycomic profile in a "reverse genomics" workflow. Toward developing this workflow we enriched Golgi membranes from two human colon cancer cell lines by sucrose density centrifugation and further mass-based fractionation by SDS-PAGE. We then applied mass spectrometry to demonstrate a doubling in the number of Golgi resident proteins identified, compared to the unenriched, low speed centrifuged supernatant of lysed cells. A total of 35 Golgi-resident glycosylation enzymes, of which 23 were glycosyltransferases, were identified making this the largest protein database so far of Golgi resident glycosylation enzymes experimentally identified in cultured human cells. We developed targeted mass spectrometry assays for specific quantitation of many of these glycosylation enzymes. Our results show that alterations in abundance of glycosylation enzymes at the protein level were generally consistent with the resultant glycomic profiles, but not necessarily with the corresponding glycosyltransferase mRNA expression as exemplified by the case of O-glycan core 1 T synthase.

  11. Glycogenomics as a mass spectrometry-guided genome-mining method for microbial glycosylated molecules.

    Science.gov (United States)

    Kersten, Roland D; Ziemert, Nadine; Gonzalez, David J; Duggan, Brendan M; Nizet, Victor; Dorrestein, Pieter C; Moore, Bradley S

    2013-11-19

    Glycosyl groups are an essential mediator of molecular interactions in cells and on cellular surfaces. There are very few methods that directly relate sugar-containing molecules to their biosynthetic machineries. Here, we introduce glycogenomics as an experiment-guided genome-mining approach for fast characterization of glycosylated natural products (GNPs) and their biosynthetic pathways from genome-sequenced microbes by targeting glycosyl groups in microbial metabolomes. Microbial GNPs consist of aglycone and glycosyl structure groups in which the sugar unit(s) are often critical for the GNP's bioactivity, e.g., by promoting binding to a target biomolecule. GNPs are a structurally diverse class of molecules with important pharmaceutical and agrochemical applications. Herein, O- and N-glycosyl groups are characterized in their sugar monomers by tandem mass spectrometry (MS) and matched to corresponding glycosylation genes in secondary metabolic pathways by a MS-glycogenetic code. The associated aglycone biosynthetic genes of the GNP genotype then classify the natural product to further guide structure elucidation. We highlight the glycogenomic strategy by the characterization of several bioactive glycosylated molecules and their gene clusters, including the anticancer agent cinerubin B from Streptomyces sp. SPB74 and an antibiotic, arenimycin B, from Salinispora arenicola CNB-527.

  12. N-Glycosylation of Lipocalin 2 Is Not Required for Secretion or Exosome Targeting

    Directory of Open Access Journals (Sweden)

    Erawan Borkham-Kamphorst

    2018-04-01

    Full Text Available Lipocalin 2 (LCN2 is a highly conserved secreted adipokine acting as a serum transport protein for small hydrophobic molecules such as fatty acids and steroids. In addition, LCN2 limits bacterial growth by sequestering iron-containing siderophores and further protects against intestinal inflammation and tumorigenesis associated with alterations in the microbiota. Human LCN2 contains one N-glycosylation site conserved in other species. It was postulated that this post-translational modification could facilitate protein folding, protects from proteolysis, is required for proper trafficking from the Golgi apparatus to the cell surface, and might be relevant for effective secretion. We here show that the homologous nucleoside antibiotic tunicamycin blocks N-linked glycosylation but not secretion of LCN2 in primary murine hepatocytes, derivatives thereof, human lung carcinoma cell line A549, and human prostate cancer cell line PC-3. Moreover, both the glycosylated and the non-glycosylated LCN2 variants are equally targeted to exosomes, demonstrating that this post-translational modification is not necessary for proper trafficking of LCN2 into these membranous extracellular vesicles. Furthermore, a hydrophobic cluster analysis revealed that the N-glycosylation site is embedded in a highly hydrophobic evolutionarily conserved surrounding. In sum, our data indicate that the N-glycosylation of LCN2 is not required for proper secretion and exosome cargo recruitment in different cell types, but might be relevant to increase overall solubility.

  13. Radionuclide therapy of endocrine-related cancer

    International Nuclear Information System (INIS)

    Kratochwil, C.; Giesel, F.L.

    2014-01-01

    This article gives an overview of the established radionuclide therapies for endocrine-related cancer that already have market authorization or are currently under evaluation in clinical trials. Radioiodine therapy is still the gold standard for differentiated iodine-avid thyroid cancer. In patients with bone and lung metastases (near) total remission is seen in approximately 50 % and the 15-year survival rate for these patients is approximately 90 %. In contrast to the USA, meta-iodobenzylguanidine (MIBG) therapy has market approval in Europe. According to the current literature, in the setting of advanced stage neuroblastoma and malignant pheochromocytoma or paraganglioma, radiological remission can be achieved in > 30 % and symptom control in almost 80 % of the treated patients. Somatostatin receptor targeted radionuclide therapies (e.g. with DOTATATE or DOTATOC) demonstrated promising results in phase 2 trials, reporting progression-free survival in the range of 24-36 months. A first phase 3 pivotal trial for intestinal carcinoids is currently recruiting and another trial for pancreatic neuroendocrine tumors is planned. Radiopharmaceuticals based on glucagon-like peptide 1 (GLP1) or minigastrins are in the early evaluation stage for application in the treatment of insulinomas and medullary thyroid cancer. In general, radiopharmaceutical therapy belongs to the group of so-called theranostics which means that therapy is tailored for individual patients based on molecular imaging diagnostics to stratify target positive or target negative tumor phenotypes. (orig.) [de

  14. Relation of microalbuminuria to glycosylated hemoglobin and ...

    African Journals Online (AJOL)

    Background: Nephropathy is one of the complications of type 2 diabetes ... Materials and Methods: Study was conducted at Medical College, Kolkata. ... Results: Urinary microalbumin, HbA1c levels were significantly higher in the cases.

  15. Relation of microalbuminuria to glycosylated hemoglobin and ...

    African Journals Online (AJOL)

    2012-04-22

    Apr 22, 2012 ... between HbA1c and microalbuminuria with the duration of diabetes is not clear. ... the detection of increased urinary microalbumin levels at the initial stage can avert, ..... haemoglobin and Lipid Profile in Diabetic Retinopathy.

  16. Optimization of a colorimetric assay for glycosylated human serum albumin

    International Nuclear Information System (INIS)

    Bohney, J.P.; Feldhoff, R.C.

    1986-01-01

    The thiobarbituric acid (TBA) assay has been used for several years to quantitate the amount of glucose which has been non-enzymatically linked to hemoglobin and other proteins. The ketoamine-protein adduct is converted to 5-hydroxymethylfurfural (HMF) by mild hydrolysis with oxalic acid. Reaction of HMF with TBA yields a colored product which has an absorbance maximum at 443 nm. Several modifications of the original procedure has been published, but none permit the unambiguous quantitation of glycosylated human serum albumin (glc-HSA). Problems relate to reagent preparation and stability, the time and temperature of hydrolysis, the choice of standards, and background color corrections. The authors have found that maximum color yield occurs after hydrolysis in an autoclave for 2 h. This increases the sensitivity 3-fold and cuts the assay time in half relative to hydrolysis for 4.5 h at 100 0 C. A NaBH 4 reduction of a parallel protein sample must be performed to correct for variable background color associated with different sample sources and amounts. HMF can be used as a standard, however, corrections must be made for HMF degradation. Fructose is a better standard, but HMF formation from fructose is faster than formation from glc-HSA. This may result in an underestimate of percent glycosylation. The best standard appears to be glc-HSA prepared with [ 3 H]glucose. It appears that with proper controls and standards the TBA assay can be used to determine actual rather than relative percent glycosylation

  17. Targeting breast cancer outcomes-what about the primary relatives?

    LENUS (Irish Health Repository)

    Johnston, Alison

    2017-07-01

    Up to 65% of newly diagnosed breast cancer patients had not been screened correctly before diagnosis resulting in increased stage of cancer at presentation. This study assessed whether their primary relatives are, in turn, assessed appropriately.

  18. Porcine dentin sialoprotein glycosylation and glycosaminoglycan attachments.

    Science.gov (United States)

    Yamakoshi, Yasuo; Nagano, Takatoshi; Hu, Jan Cc; Yamakoshi, Fumiko; Simmer, James P

    2011-02-03

    Dentin sialophosphoprotein (Dspp) is a multidomain, secreted protein that is critical for the formation of tooth dentin. Mutations in DSPP cause inherited dentin defects categorized as dentin dysplasia type II and dentinogenesis imperfecta type II and type III. Dentin sialoprotein (Dsp), the N-terminal domain of dentin sialophosphoprotein (Dspp), is a highly glycosylated proteoglycan, but little is known about the number, character, and attachment sites of its carbohydrate moieties. To identify its carbohydrate attachment sites we isolated Dsp from developing porcine molars and digested it with endoproteinase Glu-C or pronase, fractionated the digestion products, identified fractions containing glycosylated peptides using a phenol sulfuric acid assay, and characterized the glycopeptides by N-terminal sequencing, amino acid analyses, or LC/MSMS. To determine the average number of sialic acid attachments per N-glycosylation, we digested Dsp with glycopeptidase A, labeled the released N-glycosylations with 2-aminobenzoic acid, and quantified the moles of released glycosylations by comparison to labeled standards of known concentration. Sialic acid was released by sialidase digestion and quantified by measuring β-NADH reduction of pyruvic acid, which was generated stoichiometrically from sialic acid by aldolase. To determine its forms, sialic acid released by sialidase digestion was labeled with 1,2-diamino-4,5-methyleneoxybenzene (DMB) and compared to a DMB-labeled sialic acid reference panel by RP-HPLC. To determine the composition of Dsp glycosaminoglycan (GAG) attachments, we digested Dsp with chondroitinase ABC and compared the chromotagraphic profiles of the released disaccharides to commercial standards. N-glycosylations were identified at Asn37, Asn77, Asn136, Asn155, Asn161, and Asn176. Dsp averages one sialic acid per N-glycosylation, which is always in the form of N-acetylneuraminic acid. O-glycosylations were tentatively assigned at Thr200, Thr216 and Thr

  19. Porcine dentin sialoprotein glycosylation and glycosaminoglycan attachments

    Directory of Open Access Journals (Sweden)

    Yamakoshi Fumiko

    2011-02-01

    Full Text Available Abstract Background Dentin sialophosphoprotein (Dspp is a multidomain, secreted protein that is critical for the formation of tooth dentin. Mutations in DSPP cause inherited dentin defects categorized as dentin dysplasia type II and dentinogenesis imperfecta type II and type III. Dentin sialoprotein (Dsp, the N-terminal domain of dentin sialophosphoprotein (Dspp, is a highly glycosylated proteoglycan, but little is known about the number, character, and attachment sites of its carbohydrate moieties. Results To identify its carbohydrate attachment sites we isolated Dsp from developing porcine molars and digested it with endoproteinase Glu-C or pronase, fractionated the digestion products, identified fractions containing glycosylated peptides using a phenol sulfuric acid assay, and characterized the glycopeptides by N-terminal sequencing, amino acid analyses, or LC/MSMS. To determine the average number of sialic acid attachments per N-glycosylation, we digested Dsp with glycopeptidase A, labeled the released N-glycosylations with 2-aminobenzoic acid, and quantified the moles of released glycosylations by comparison to labeled standards of known concentration. Sialic acid was released by sialidase digestion and quantified by measuring β-NADH reduction of pyruvic acid, which was generated stoichiometrically from sialic acid by aldolase. To determine its forms, sialic acid released by sialidase digestion was labeled with 1,2-diamino-4,5-methyleneoxybenzene (DMB and compared to a DMB-labeled sialic acid reference panel by RP-HPLC. To determine the composition of Dsp glycosaminoglycan (GAG attachments, we digested Dsp with chondroitinase ABC and compared the chromotagraphic profiles of the released disaccharides to commercial standards. N-glycosylations were identified at Asn37, Asn77, Asn136, Asn155, Asn161, and Asn176. Dsp averages one sialic acid per N-glycosylation, which is always in the form of N-acetylneuraminic acid. O-glycosylations were

  20. Tobacco and Alcohol in Relation to Male Breast Cancer

    DEFF Research Database (Denmark)

    Cook, Michael B; Guénel, Pascal; Gapstur, Susan M

    2015-01-01

    BACKGROUND: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. METHODS: The Male Breast Cancer Pooling Project consortium prov...

  1. A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

    Energy Technology Data Exchange (ETDEWEB)

    Kalra, Rajkumar S., E-mail: renu-wadhwa@aist.go.jp; Wadhwa, Renu, E-mail: renu-wadhwa@aist.go.jp [Cell Proliferation Research Group and DBT-AIST International Laboratory for Advanced Biomedicine, National Institute of Advanced Industrial Science and Technology (AIST Central 4), 1-1-1 Higashi, Tsukuba, Ibaraki 305-8562 (Japan)

    2015-02-27

    Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylation target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein.

  2. A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

    International Nuclear Information System (INIS)

    Kalra, Rajkumar S.; Wadhwa, Renu

    2015-01-01

    Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylation target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein

  3. Basic research on cancer related to radiation associated medical researches

    International Nuclear Information System (INIS)

    Lee, Jong In; Hwang, Dae Yong; Bang, Ho Yoon

    2000-12-01

    Basic Research on Cancer related to Radiation Associated Medical Researches including 1. Establishment of animal model of colorectal cancer liver metastasis and measurement of angiogenesis, 2. Tissue expression of Tie-1 and Tie-2 in human colorectal cancer, 3. Enhancement of G2/Mphase Cell Fraction by Adenovirus-mediated p53 Gene Transfer in Ovarian Cancer Cell Lines, 4. Clinical Characteristics of the patients with Non-B Non-C Hepatocellular Carcinoma and Frequency of HBV, HCV and TTV Viremia in these Patients, 5. Significance of serum iron and ferritin in patients with stomach cancer, 6. Telomerase assay for early detection of lung cancer, 7. Study on the Usefulness of Aldehyde dehydrogenase-2 Genotyping for Risk Group of Alcohol-related Cancer Screening, 8. Gene therapy using hepatoma specific promoter, 9. Study on the Influence of DNA repair gene, XRCC1 Genotypes on the Risk of Head and Neck Cancer were performed

  4. Basic research on cancer related to radiation associated medical researches

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong In; Hwang, Dae Yong; Bang, Ho Yoon [and others

    2000-12-01

    Basic Research on Cancer related to Radiation Associated Medical Researches including 1. Establishment of animal model of colorectal cancer liver metastasis and measurement of angiogenesis, 2. Tissue expression of Tie-1 and Tie-2 in human colorectal cancer, 3. Enhancement of G2/Mphase Cell Fraction by Adenovirus-mediated p53 Gene Transfer in Ovarian Cancer Cell Lines, 4. Clinical Characteristics of the patients with Non-B Non-C Hepatocellular Carcinoma and Frequency of HBV, HCV and TTV Viremia in these Patients, 5. Significance of serum iron and ferritin in patients with stomach cancer, 6. Telomerase assay for early detection of lung cancer, 7. Study on the Usefulness of Aldehyde dehydrogenase-2 Genotyping for Risk Group of Alcohol-related Cancer Screening, 8. Gene therapy using hepatoma specific promoter, 9. Study on the Influence of DNA repair gene, XRCC1 Genotypes on the Risk of Head and Neck Cancer were performed.

  5. NetOglyc: prediction of mucin type O-glycosylation sites based on sequence context and surface accessibility

    DEFF Research Database (Denmark)

    Hansen, Jan Erik; Lund, Ole; Tolstrup, Niels

    1998-01-01

    -glycosylated serine and threonine residues in independent test sets, thus proving more accurate than matrix statistics and vector projection methods. Predicition of O-glycosylation sites in the envelope glycoprotein gp120 from the primate lentiviruses HIV-1, HIV-2 and SIV are presented. The most conserved O...... structure and surface accessibility. The sequence context of glycosylated threonines was found to differ from that of serine, and the sites were found to cluster. Non-clustered sites had a sequence context different from that of clustered sites. charged residues were disfavoured at postition -1 and +3......-glycosylation signals in these evolutionary-related glycoproteins were found in their first hypervariable loop, V1. However, the strain variation for HIV-1 gp120 was significant. A computer server, available through WWW or E-mail, has been developed for prediction of mucin type O-glycosylation sites in proteins based...

  6. Aberrant Glycosylation in the Left Ventricle and Plasma of Rats with Cardiac Hypertrophy and Heart Failure.

    Directory of Open Access Journals (Sweden)

    Chiaki Nagai-Okatani

    Full Text Available Targeted proteomics focusing on post-translational modifications, including glycosylation, is a useful strategy for discovering novel biomarkers. To apply this strategy effectively to cardiac hypertrophy and resultant heart failure, we aimed to characterize glycosylation profiles in the left ventricle and plasma of rats with cardiac hypertrophy. Dahl salt-sensitive hypertensive rats, a model of hypertension-induced cardiac hypertrophy, were fed a high-salt (8% NaCl diet starting at 6 weeks. As a result, they exhibited cardiac hypertrophy at 12 weeks and partially impaired cardiac function at 16 weeks compared with control rats fed a low-salt (0.3% NaCl diet. Gene expression analysis revealed significant changes in the expression of genes encoding glycosyltransferases and glycosidases. Glycoproteome profiling using lectin microarrays indicated upregulation of mucin-type O-glycosylation, especially disialyl-T, and downregulation of core fucosylation on N-glycans, detected by specific interactions with Amaranthus caudatus and Aspergillus oryzae lectins, respectively. Upregulation of plasma α-l-fucosidase activity was identified as a biomarker candidate for cardiac hypertrophy, which is expected to support the existing marker, atrial natriuretic peptide and its related peptides. Proteomic analysis identified cysteine and glycine-rich protein 3, a master regulator of cardiac muscle function, as an O-glycosylated protein with altered glycosylation in the rats with cardiac hypertrophy, suggesting that alternations in O-glycosylation affect its oligomerization and function. In conclusion, our data provide evidence of significant changes in glycosylation pattern, specifically mucin-type O-glycosylation and core defucosylation, in the pathogenesis of cardiac hypertrophy and heart failure, suggesting that they are potential biomarkers for these diseases.

  7. Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1

    International Nuclear Information System (INIS)

    Watanabe, Ayahisa; Nishijima, Ken-ichi; Zhao, Songji; Tamaki, Nagara; Kuge, Yuji; Tanaka, Yoshikazu; Itoh, Takeshi; Takemoto, Hiroshi

    2012-01-01

    Glycosylation is generally applicable as a strategy for increasing the activity of bioactive proteins. In this study, we examined the effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1 (GLP-1) as a bioactive peptide for type 2 diabetes. Noninvasive imaging studies were performed using a gamma camera after the intravenous administration of 123 I-GLP-1 or 123 I-α2, 6-sialyl N-acetyllactosamine (glycosylated) GLP-1 in rats. In ex vivo biodistribution studies using 125 I-GLP-1 or 125 I-glycosylated GLP-1, organ samples were measured for radioactivity. Plasma samples were added to 15% trichloroacetic acid (TCA) to obtain TCA-insoluble and TCA-soluble fractions. The radioactivity in the TCA-insoluble and TCA-soluble fractions was measured. In the noninvasive imaging studies, a relatively high accumulation level of 123 I-GLP-1 was found in the liver, which is the major organ to eliminate exogenous GLP-1. The area under the time-activity curve (AUC) of 123 I-glycosylated GLP-1 in the liver was significantly lower (89%) than that of 123 I-GLP-1. These results were consistent with those of ex vivo biodistribution studies using 125 I-labeled peptides. The AUC of 125 I-glycosylated GLP-1 in the TCA-insoluble fraction was significantly higher (1.7-fold) than that of GLP-1. This study demonstrated that glycosylation significantly decreased the distribution of radiolabeled GLP-1 into the liver and increased the concentration of radiolabeled GLP-1 in plasma. These results suggested that glycosylation is a useful strategy for decreasing the distribution into the liver of bioactive peptides as desirable pharmaceuticals. (author)

  8. Pregnancy-related venous thromboembolism and risk of occult cancer

    DEFF Research Database (Denmark)

    Tarp Hansen, Anette; Veres, Katalin; Horváth-Puhó, Erzsébet

    2017-01-01

    The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected.An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk.......The cancer risk during the first year after a pregnancy-related venous thromboembolism episode is higher than expected.An aggressive search for cancer in women with pregnancy-related venous thromboembolism is probably not warranted, due to low absolute risk....

  9. Epidemiology of cancer-related venous thromboembolism

    OpenAIRE

    Wun, Ted; White, Richard H.

    2009-01-01

    Recent studies have better defined the epidemiology of venous thromboembolism (VTE) in cancer patients. The incidence is highest in patients who have metastatic disease at the time of presentation and who have fast growing, biologically aggressive cancers associated with a poor prognosis. The incidence is also high in patients with haematological cancers. Other specific risk factors that affect the incidence of VTE include undergoing invasive neurosurgery, the number of underlying chronic co-...

  10. Unmodifiable variables related to thyroid cancer incidence

    OpenAIRE

    Cornelia Nitipir; Lucian Alecu; Iulian Slavu; Raluca Tulin; Radu C. Jecan

    2018-01-01

    The incidence of thyroid cancer is significantly different between male and female patients. Thyroid cancer is also the only form of cancer where age can be considered a staging variable. Identifying biological prognostic factors such as age or sex is important as it helps select an optimal personalized therapy. The present analysis is an observational, prospective study that enrolled all patients with thyroid disease who were operated upon at a single center. The study aimed to determine the...

  11. Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis.

    Science.gov (United States)

    Vermassen, Tijl; Van Praet, Charles; Poelaert, Filip; Lumen, Nicolaas; Decaestecker, Karel; Hoebeke, Piet; Van Belle, Simon; Rottey, Sylvie; Delanghe, Joris

    2015-01-01

    Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N=66) and prostatitis patients (N=36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (Pprostatitis patients from HV (Pprostatitis patients compared to HV (Pprostatitis. Further research is required to unravel the developmental course of prostatic inflammation.

  12. Fasting serum glucose and glycosylated hemoglobin level in obesity.

    Science.gov (United States)

    Das, R K; Nessa, A; Hossain, M A; Siddiqui, N I; Hussain, M A

    2014-04-01

    Obesity is a condition in which the body fat stores are increased to an extent which impairs health and leads to serious health consequences. The amount of body fat is difficult to measure directly, and is usually determined from an indirect measure - the body mass index (BMI). Increased BMI in obese persons is directly associated with an increase in metabolic disease, such as type 2 diabetes mellitus. This Analytical cross sectional study was undertaken to assess the relation between obesity and glycemic control of body by measuring fasting serum glucose and glycosylated hemoglobin. This study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh from 1st July 2011 to 30th June 2012 on 120 equally divided male and female persons within the age range of 25 to 55 years. Age more than 55 years and less than 25 years and diagnosed case of Hypothyroidism, Cushing's syndrome, polycystic ovary, Antipsychotic drug user and regular steroid users were excluded. Non probability purposive type of sampling technique was used for selecting the study subjects. Measurement of body mass index was done as per procedure. Fasting serum glucose was estimated by glucose oxidase method and Glycosylated hemoglobin by Boronate Affinity method. Statistical analysis was done by SPSS (version 17.0). Data were expressed as Mean±SE and statistical significance of difference among the groups were calculated by unpaired student's 't' test and Pearson's correlation coefficient tests were done as applicable. The Mean±SE of fasting serum glucose was significant at 1% level (P value obese group of BMI. There was no significant difference of glycosylated hemoglobin level between control and study groups. But there was positive correlation within each group. Fasting serum glucose also showed a bit stronger positive correlation with BMI. Both obese male and female persons showed higher levels of fasting serum glucose and glycosylated hemoglobin. The observed positive

  13. Posttraumatic Stress Disorder Among Bereaved Relatives of Cancer Patients

    DEFF Research Database (Denmark)

    Elklit, Ask; Reinholt, N.; Nielsen, Louise Hjort

    2010-01-01

    The aim of this study was to assess post-traumatic stress disorder (PTSD) and predictors of PTSD in individuals who experienced the loss of a close relative to cancer. A total of 251 bereaved relatives ages 14 to 76 (M = 41.3, SD = 16.8) were recruited at a counseling service for cancer patients...

  14. Classification of treatment-related mortality in children with cancer

    DEFF Research Database (Denmark)

    Alexander, Sarah; Pole, Jason D; Gibson, Paul

    2015-01-01

    Treatment-related mortality is an important outcome in paediatric cancer clinical trials. An international group of experts in supportive care in paediatric cancer developed a consensus-based definition of treatment-related mortality and a cause-of-death attribution system. The reliability and va...

  15. Cancer in first-degree relatives and risk of testicular cancer in Denmark

    Science.gov (United States)

    Nordsborg, Rikke Baastrup; Meliker, Jaymie R.; Wohlfahrt, Jan; Melbye, Mads; Raaschou-Nielsen, Ole

    2011-01-01

    Familial aggregation of testicular cancer has been reported consistently, but it is less clear if there is any association between risk of testicular cancer and other cancers in the family. We conducted a population based case-control study to examine the relationship between risk of testicular cancer and 22 different cancers in first-degree relatives. We included 3297 cases of testicular cancer notified to the Danish Cancer Registry between 1991 and 2003. 6594 matched controls were selected from the Danish Civil Registration System, which also provided the identity of 40,104 first-degree relatives of case and controls. Familial cancer was identified by linkage to the Danish Cancer Registry, and we used conditional logistic regression to analyse whether cancer among first-degree relatives was associated with higher risk of testicular cancer. Rate ratio (RR) for testicular cancer was 4.63 (95% CI: 2.41–8.87) when a father, 8.30(95% CI: 3.81–18.10) when a brother and 5.23 (95% CI: 1.35–20.26) when a son had testicular cancer compared with no familial testicular cancer. Results were similar when analyses were stratified by histologic subtypes of testicular cancer. Familial Non-Hodgkin lymphoma and oesophageal cancer were associated with testicular cancer; however these may be chance findings. The familial aggregation of testicular and possibly other cancers may be explained by shared genes and/or shared environmental factors, but the mutual importance of each of these is difficult to determine. PMID:21207375

  16. Cancer-related fatigue: Mechanisms, risk factors, and treatments

    Science.gov (United States)

    Bower, Julienne E.

    2015-01-01

    Fatigue is one of the most common and distressing side effects of cancer and its treatment, and may persist for years after treatment completion in otherwise healthy survivors. Cancer-related fatigue causes disruption in all aspects of quality of life and may be a risk factor for reduced survival. The prevalence and course of fatigue in cancer patients has been well characterized, and there is growing understanding of underlying biological mechanisms. Inflammation has emerged as a key biological pathway for cancer-related fatigue, with studies documenting links between markers of inflammation and fatigue before, during, and particularly after treatment. There is considerable variability in the experience of cancer-related fatigue that is not explained by disease- or treatment-related characteristics, suggesting that host factors may play an important role in the development and persistence of this symptom. Indeed, longitudinal studies have begun to identify genetic, biological, psychosocial, and behavioral risk factors for cancer-related fatigue. Given the multi-factorial nature of cancer-related fatigue, a variety of intervention approaches have been examined in randomized controlled trials, including physical activity, psychosocial, mind-body, and pharmacological treatments. Although there is currently no gold standard for treating fatigue, several of these approaches have shown beneficial effects and can be recommended to patients. This report provides a state of the science review of mechanisms, risk factors, and interventions for cancer-related fatigue, with a focus on recent longitudinal studies and randomized trials that have targeted fatigued patients. PMID:25113839

  17. fasting blood glucose and glycosylated haemoglobin levels

    African Journals Online (AJOL)

    Prince Acheampong

    (HbA1c) levels of diabetes mellitus patients as an index of glycaemic control. It was a prospective case- finding study using laboratory and general practice records. ... range of glycosylated haemoglobins, and the cut-off values for some clinical .... quality of glycaemic control by glycated haemoglobin in out-patient diabetic ...

  18. Is glycosylated haemoglobin a marker of fertility?

    DEFF Research Database (Denmark)

    Hjollund, N H; Jensen, Tina Kold; Bonde, Jens Peter

    1999-01-01

    We performed a follow-up study of time to pregnancy in a population of first-time pregnancy planners without previous reproductive experience. The objective of this paper is to report and discuss a finding of a strong relationship between glycosylated haemoglobin (HbA1C) and fertility. A total...

  19. The relation between the anthropometric characteristics of fingers and cancer

    Directory of Open Access Journals (Sweden)

    Omid Mardanshahi

    2017-07-01

    Full Text Available Anthropometry is a science of human body measurement that could be used for manufacturing artificial limbs or prosthesis, investigating body differences between populations, utilizing in forensics and criminology, or even in the diagnosis of some diseases. Two of the most important anthropometric characteristics are dermatoglyphic patterns and finger length. Many studies have evaluated the relation between these two characteristics in different diseases such as cancers. It assumed that dermatoglyphic patterns and finger length could be used as predictors of some cancers such as gastric, ovarian, prostate, testicular, and breast cancers. In this review, we evaluated the relation between dermatoglyphic variability and finger length in different cancers more precisely.

  20. Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling

    Directory of Open Access Journals (Sweden)

    Inês Gomes Ferreira

    2018-02-01

    Full Text Available Glycosylation is a very frequent and functionally important post-translational protein modification that undergoes profound changes in cancer. Growth and death factor receptors and plasma membrane glycoproteins, which upon activation by extracellular ligands trigger a signal transduction cascade, are targets of several molecular anti-cancer drugs. In this review, we provide a thorough picture of the mechanisms bywhich glycosylation affects the activity of growth and death factor receptors in normal and pathological conditions. Glycosylation affects receptor activity through three non-mutually exclusive basic mechanisms: (1 by directly regulating intracellular transport, ligand binding, oligomerization and signaling of receptors; (2 through the binding of receptor carbohydrate structures to galectins, forming a lattice thatregulates receptor turnover on the plasma membrane; and (3 by receptor interaction with gangliosides inside membrane microdomains. Some carbohydrate chains, for example core fucose and β1,6-branching, exert a stimulatory effect on all receptors, while other structures exert opposite effects on different receptors or in different cellular contexts. In light of the crucial role played by glycosylation in the regulation of receptor activity, the development of next-generation drugs targeting glyco-epitopes of growth factor receptors should be considered a therapeutically interesting goal.

  1. Surface glycosylation profiles of urine extracellular vesicles.

    Directory of Open Access Journals (Sweden)

    Jared Q Gerlach

    Full Text Available Urinary extracellular vesicles (uEVs are released by cells throughout the nephron and contain biomolecules from their cells of origin. Although uEV-associated proteins and RNA have been studied in detail, little information exists regarding uEV glycosylation characteristics. Surface glycosylation profiling by flow cytometry and lectin microarray was applied to uEVs enriched from urine of healthy adults by ultracentrifugation and centrifugal filtration. The carbohydrate specificity of lectin microarray profiles was confirmed by competitive sugar inhibition and carbohydrate-specific enzyme hydrolysis. Glycosylation profiles of uEVs and purified Tamm Horsfall protein were compared. In both flow cytometry and lectin microarray assays, uEVs demonstrated surface binding, at low to moderate intensities, of a broad range of lectins whether prepared by ultracentrifugation or centrifugal filtration. In general, ultracentrifugation-prepared uEVs demonstrated higher lectin binding intensities than centrifugal filtration-prepared uEVs consistent with lesser amounts of co-purified non-vesicular proteins. The surface glycosylation profiles of uEVs showed little inter-individual variation and were distinct from those of Tamm Horsfall protein, which bound a limited number of lectins. In a pilot study, lectin microarray was used to compare uEVs from individuals with autosomal dominant polycystic kidney disease to those of age-matched controls. The lectin microarray profiles of polycystic kidney disease and healthy uEVs showed differences in binding intensity of 6/43 lectins. Our results reveal a complex surface glycosylation profile of uEVs that is accessible to lectin-based analysis following multiple uEV enrichment techniques, is distinct from co-purified Tamm Horsfall protein and may demonstrate disease-specific modifications.

  2. Recent declines in cancer incidence: related to the Great Recession?

    Science.gov (United States)

    Gomez, Scarlett Lin; Canchola, Alison J; Nelson, David O; Keegan, Theresa H M; Clarke, Christina A; Cheng, Iona; Shariff-Marco, Salma; DeRouen, Mindy; Catalano, Ralph; Satariano, William A; Davidson-Allen, Kathleen; Glaser, Sally L

    2017-02-01

    In recent years, cancer case counts in the U.S. underwent a large, rapid decline-an unexpected change given population growth for older persons at highest cancer risk. As these declines coincided with the Great Recession, we examined whether they were related to economic conditions. Using California Cancer Registry data from California's 30 most populous counties, we analyzed trends in cancer incidence during pre-recession (1996-2007) and recession/recovery (2008-2012) periods for all cancers combined and the ten most common sites. We evaluated the recession's association with rates using a multifactorial index that measured recession impact, and modeled associations between case counts and county-level unemployment rates using Poisson regression. Yearly cancer incidence rate declines were greater during the recession/recovery (3.3% among males, 1.4% among females) than before (0.7 and 0.5%, respectively), particularly for prostate, lung, and colorectal cancers. Lower case counts, especially for prostate and liver cancer among males and breast cancer, melanoma, and ovarian cancer among females, were associated with higher unemployment rates, irrespective of time period, but independent of secular effects. The associations for melanoma translated up to a 3.6% decrease in cases with each 1% increase in unemployment. Incidence declines were not greater in counties with higher recession impact index. Although recent declines in incidence of certain cancers are not differentially impacted by economic conditions related to the Great Recession relative to pre-recession conditions, the large recent absolute declines in the case counts of some cancer may be attributable to the large declines in unemployment in the recessionary period. This may occur through decreased engagement in preventive health behaviors, particularly for clinically less urgent cancers. Continued monitoring of trends is important to detect any rises in incidence rates as deferred diagnoses come to

  3. Optimization of a colorimetric assay for glycosylated human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Bohney, J.P.; Feldhoff, R.C.

    1986-05-01

    The thiobarbituric acid (TBA) assay has been used for several years to quantitate the amount of glucose which has been non-enzymatically linked to hemoglobin and other proteins. The ketoamine-protein adduct is converted to 5-hydroxymethylfurfural (HMF) by mild hydrolysis with oxalic acid. Reaction of HMF with TBA yields a colored product which has an absorbance maximum at 443 nm. Several modifications of the original procedure has been published, but none permit the unambiguous quantitation of glycosylated human serum albumin (glc-HSA). Problems relate to reagent preparation and stability, the time and temperature of hydrolysis, the choice of standards, and background color corrections. The authors have found that maximum color yield occurs after hydrolysis in an autoclave for 2 h. This increases the sensitivity 3-fold and cuts the assay time in half relative to hydrolysis for 4.5 h at 100/sup 0/C. A NaBH/sub 4/ reduction of a parallel protein sample must be performed to correct for variable background color associated with different sample sources and amounts. HMF can be used as a standard, however, corrections must be made for HMF degradation. Fructose is a better standard, but HMF formation from fructose is faster than formation from glc-HSA. This may result in an underestimate of percent glycosylation. The best standard appears to be glc-HSA prepared with (/sup 3/H)glucose. It appears that with proper controls and standards the TBA assay can be used to determine actual rather than relative percent glycosylation.

  4. Prion Propagation in Cells Expressing PrP Glycosylation Mutants ▿

    Science.gov (United States)

    Salamat, Muhammad K.; Dron, Michel; Chapuis, Jérôme; Langevin, Christelle; Laude, Hubert

    2011-01-01

    Infection by prions involves conversion of a host-encoded cell surface protein (PrPC) to a disease-related isoform (PrPSc). PrPC carries two glycosylation sites variably occupied by complex N-glycans, which have been suggested by previous studies to influence the susceptibility to these diseases and to determine characteristics of prion strains. We used the Rov cell system, which is susceptible to sheep prions, to generate a series of PrPC glycosylation mutants with mutations at one or both attachment sites. We examined their subcellular trafficking and ability to convert into PrPSc and to sustain stable prion propagation in the absence of wild-type PrP. The susceptibility to infection of mutants monoglycosylated at either site differed dramatically depending on the amino acid substitution. Aglycosylated double mutants showed overaccumulation in the Golgi compartment and failed to be infected. Introduction of an ectopic glycosylation site near the N terminus fully restored cell surface expression of PrP but not convertibility into PrPSc, while PrPC with three glycosylation sites conferred cell permissiveness to infection similarly to the wild type. In contrast, predominantly aglycosylated molecules with nonmutated N-glycosylation sequons, produced in cells expressing glycosylphosphatidylinositol-anchorless PrPC, were able to form infectious PrPSc. Together our findings suggest that glycosylation is important for efficient trafficking of anchored PrP to the cell surface and sustained prion propagation. However, properly trafficked glycosylation mutants were not necessarily prone to conversion, thus making it difficult in such studies to discern whether the amino acid changes or glycan chain removal most influences the permissiveness to prion infection. PMID:21248032

  5. Relatives' level of satisfaction with advanced cancer care in Greenland

    DEFF Research Database (Denmark)

    Augustussen, Mikaela; Hounsgaard, Lise; Pedersen, Michael Lynge

    2017-01-01

    Palliative cancer care in Greenland is provided by health professionals at local level, the national Queen Ingrid's Hospital and at Rigshospitalet in Denmark. To improve and develop care for relatives of patients with advanced cancer, we conducted a mixed method study examining relatives' level...... of satisfaction with care and treatment and their current main concerns. The aim was to investigate relatives' level of satisfaction with advanced cancer care and bring to light their current main concerns. The FAMCARE-20 questionnaire was translated to Greenlandic and pilot tested. The questionnaire...... (66%) and relatives were the most dissatisfied with the lack of inclusion in decision making related to treatment and care (71%) and the length of time required to diagnose cancer (70%). Responses to the open-ended questions revealed that relatives faced challenges in gaining access to information...

  6. [Cancer related fatigue in patients with breast cancer after chemotherapy and coping style].

    Science.gov (United States)

    Jiang, Pinglan; Wang, Shuhong; Jiang, Dongmei; Yu, Lingli

    2011-04-01

    To study the relevance between cancer related fatigue and coping styles in breast cancer patients after chemotherapy. A survey was conducted in 396 patients with breast cancer after chemotherapy on cancer related fatigue scale and Jalowiec coping scale, and the relation was analyzed. The rate of overall fatigue in breast cancer patients was 96.97%, mostly moderate fatigue. The rate of fatigue dimensions from high to low was physical fatigue, feeling fatigue and cognitive fatigue, respectively. The score of coping styles in patients with breast cancer after chemotherapy from high to low was optimistic coping, facing bravely, support seeking, self-reliance, emotional catharsis, avoidance, fatalism, and conservation. The most widely used coping style was optimistic coping style, and the least was emotional catharisis. There was a positive correlation between coping style of emotional catharsis and cancer related fatigue of all dimensions (Pself-reliance, or conservation (P<0.05). There was also a negative correlation between physical fatigue and optimistic or support seeking (P<0.05), but there was a positive correlation between avoidance or fatalism and the dimensions of general fatigue, physical fatigue, and cognitive fatigue (P<0.05). There is prevalent cancer related fatigue in patients with breast cancer after chemotherapy. We should guide the patients to more active coping styles, to enhance the ability of psychological adaption in patients, reduce cancer related fatigue, and improve the quality of life.

  7. Competition between folding and glycosylation in the endoplasmic reticulum

    DEFF Research Database (Denmark)

    Holst, B; Bruun, A W; Kielland-Brandt, Morten

    1996-01-01

    Using carboxypeptidase Y in Saccharomyces cerevisiae as a model system, the in vivo relationship between protein folding and N-glycosylation was studied. Seven new sites for N-glycosylation were introduced at positions buried in the folded protein structure. The level of glycosylation of such new...... acceptor sites. In some cases, all the newly synthesized mutant protein was modified at the novel site while in others no modification took place. In the most interesting category of mutants, the level of glycosylation was dependent on the conditions for folding. This shows that folding and glycosylation...

  8. Control of mucin-type O-glycosylation

    DEFF Research Database (Denmark)

    Bennett, Eric P; Mandel, Ulla; Clausen, Henrik

    2012-01-01

    residues, is one of the most abundant forms of protein glycosylation in animals. Although most protein glycosylation is controlled by one or two genes encoding the enzymes responsible for the initiation of glycosylation, i.e. the step where the first glycan is attached to the relevant amino acid residue...... in the protein, mucin-type O-glycosylation is controlled by a large family of up to 20 homologous genes encoding UDP-GalNAc:polypeptide GalNAc-transferases (GalNAc-Ts) (EC 2.4.1.41). Therefore, mucin-type O-glycosylation has the greatest potential for differential regulation in cells and tissues. The Gal...

  9. Projecting productivity losses for cancer-related mortality 2011 - 2030.

    Science.gov (United States)

    Pearce, Alison; Bradley, Cathy; Hanly, Paul; O'Neill, Ciaran; Thomas, Audrey Alforque; Molcho, Michal; Sharp, Linda

    2016-10-18

    When individuals stop working due to cancer this represents a loss to society - the loss of productivity. The aim of this analysis was to estimate productivity losses associated with premature mortality from all adult cancers and from the 20 highest mortality adult cancers in Ireland in 2011, and project these losses until 2030. An incidence-based method was used to estimate the cost of cancer deaths between 2011 and 2030 using the Human Capital Approach. National data were used for cancer, population and economic inputs. Both paid work and unpaid household activities were included. Sensitivity analyses estimated the impact of assumptions around future cancer mortality rates, retirement ages, value of unpaid work, wage growth and discounting. The 233,000 projected deaths from all invasive cancers in Ireland between 2011 and 2030 will result in lost productivity valued at €73 billion; €13 billion in paid work and €60 billion in household activities. These losses represent approximately 1.4 % of Ireland's GDP annually. The most costly cancers are lung (€14.4 billion), colorectal and breast cancer (€8.3 billion each). However, when viewed as productivity losses per cancer death, testis (€364,000 per death), cervix (€155,000 per death) and brain cancer (€136,000 per death) are most costly because they affect working age individuals. An annual 1 % reduction in mortality reduces productivity losses due to all invasive cancers by €8.5 billion over 20 years. Society incurs substantial losses in productivity as a result of cancer-related mortality, particularly when household production is included. These estimates provide valuable evidence to inform resource allocation decisions in cancer prevention and control.

  10. Risk of cancer in relatives of patients with myotonic dystrophy

    DEFF Research Database (Denmark)

    Lund, M; Diaz, L J; Gørtz, S

    2014-01-01

    BACKGROUND AND PURPOSE: Myotonic dystrophies (DM) are autosomal dominantly inherited neuromuscular disorders caused by unstable nucleotide repeat expansions. DM and cancer have been associated, but the pathogenesis behind the association remains unclear. It could relate to derived effects of the DM...... genotype in which case non-DM relatives of DM patients would not be expected to be at increased risk of cancer. To elucidate this, a population-based cohort study investigating risk of cancer in relatives of DM patients was conducted. METHODS: DM was identified using the National Danish Patient Registry...

  11. NAD+ Deficits in Age-Related Diseases and Cancer.

    Science.gov (United States)

    Garrido, Amanda; Djouder, Nabil

    2017-08-01

    The phenomenon of aging has gained widespread attention in recent times. Although significant advances have been made to better understand aging and its related pathologies including cancer, there is not yet a clear mechanism explaining why diseases and cancer are inherent parts of the aging process. Finding a unifying equation that could bridge aging and its related diseases would allow therapeutic development and solve an immense human health problem to live longer and better. In this review, we discuss NAD + reduction as the central mechanism that may connect aging to its related pathologies and cancer. NAD + boosters would ensure and ameliorate health quality during aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. The management of breast cancer-related lymphoedema

    African Journals Online (AJOL)

    Definition. Breast cancer-related lymphoedema (BCRL) is a secondary form of lymphoedema and a major complication of post-breast cancer surgery and radiotherapy. It occurs when the network of lymphatic vessels and lymph nodes is damaged by disease, surgery or radiotherapy. The lymph, a protein-rich fluid, then ...

  13. Breast Cancer-Related Lymphedema: Implications for Family Leisure Participation

    Science.gov (United States)

    Radina, M. Elise

    2009-01-01

    An estimated 20% of breast cancer survivors face the chronic condition of breast cancer-related lymphedema. This study explored the ways in which women with this condition experienced changes in their participation in family leisure as one indicator of family functioning. Participants (N = 27) were interviewed regarding lifestyles before and after…

  14. Cancer-related fatigue--mechanisms, risk factors, and treatments.

    Science.gov (United States)

    Bower, Julienne E

    2014-10-01

    Fatigue is one of the most common adverse effects of cancer that might persist for years after treatment completion in otherwise healthy survivors. Cancer-related fatigue causes disruption in all aspects of quality of life and might be a risk factor of reduced survival. The prevalence and course of fatigue in patients with cancer have been well characterized and there is growing understanding of the underlying biological mechanisms. Inflammation seems to have a key role in fatigue before, during, and after cancer-treatment. However, there is a considerable variability in the presentation of cancer-related fatigue, much of which is not explained by disease-related or treatment-related characteristics, suggesting that host factors might be important in the development and persistence of this symptom. Indeed, longitudinal studies have identified genetic, biological, psychosocial, and behavioural risk factors associated with cancer-related fatigue. Although no current gold-standard treatment for fatigue is available, a variety of intervention approaches have shown beneficial effects in randomized controlled trials, including physical activity, psychosocial, mind-body, and pharmacological treatments. This Review describes the mechanisms, risk factors, and possible interventions for cancer-related fatigue, focusing on recent longitudinal studies and randomized trials that have targeted fatigued patients.

  15. Relatives' level of satisfaction with advanced cancer care in Greenland

    DEFF Research Database (Denmark)

    Augustussen, Mikaela; Hounsgaard, Lise; Pedersen, Michael Lynge

    2017-01-01

    from health professionals. They experienced a lack of security, worries about the future and a lack of support at home. The study showed a substantial level of dissatisfaction among relatives of patients with advanced cancer. We strongly recommend a focus on psychosocial care, more access......Palliative cancer care in Greenland is provided by health professionals at local level, the national Queen Ingrid's Hospital and at Rigshospitalet in Denmark. To improve and develop care for relatives of patients with advanced cancer, we conducted a mixed method study examining relatives' level...... was supplemented by open-ended questions about relative's current main concerns and analyzed with a phenomenological hermeneutical approach. Greenlandic patients with advanced cancer who were previously participating in a prospective study were asked if their closest adult relative would participate in the study...

  16. Association between cancer literacy and cancer-related behaviour: evidence from Ticino, Switzerland

    Directory of Open Access Journals (Sweden)

    Nicola Diviani

    2014-07-01

    Full Text Available Background. This paper details the role of different dimensions of health literacy in the relationship between health literacy and cancer-related health behaviours. In particular, Cancer Literacy is studied as an exemplar of a dimension of health literacy beyond basic reading and writing skills. The link between functional health literacy, Cancer Literacy and cancer-related health behaviours is investigated in a sample of Ticino (Switzerland residents (n=639. Design and methods. Detailed data is collected about respondents’ functional health literacy, Cancer Literacy, cancer information seeking behaviour, engagement in cancer preventive behaviours, participation to cancer screenings, and intention to adhere to current screening recommendations. Results. Results confirm the added value of Cancer Literacy – compared to functional health literacy – in explaining people’s cancer information seeking behaviour, their participation to several cancer screenings and their screening intention, underscoring the need to take into account dimensions of health literacy beyond basic functional skills. Conclusions. From a public health perspective, findings provide further evidence on the importance of adapting informational and educational communication intervention designed to improve cancer prevention and screening to different audiences.

  17. Efficient synthesis of glycosylated phenazine natural products and analogs with DISAL (methyl 3,5-dinitrosalicylate) glycosyl donors

    DEFF Research Database (Denmark)

    Laursen, Jane B.; Petersen, Lars; Jensen, K.J.

    2003-01-01

    Inspired by the occurrence and function of phenazines in natural products, new glycosylated analogs were designed and synthesized. DISAL (methyl 3,5-dinitrosalicylate) glycosyl donors were used in an efficient and easily-handled glycosylation protocol compatible with combinatorial chemistry....... Benzoylated D-glucose, D-galactose and L-quinovose DISAL glycosyl donors were synthesized in high yields and used under mild conditions to glycosylate methyl saphenate and 2-hydroxyphenazine. The glycosides were screened for biological activity and one compound showed inhibitory activity towards topoisomerase...

  18. MicroRNA Related Polymorphisms and Breast Cancer Risk

    DEFF Research Database (Denmark)

    Khan, Sofia; Greco, Dario; Michailidou, Kyriaki

    2014-01-01

    Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer....... We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41......,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated...

  19. Congenital disorders of glycosylation: The Saudi experience.

    Science.gov (United States)

    Alsubhi, Sarah; Alhashem, Amal; Faqeih, Eissa; Alfadhel, Majid; Alfaifi, Abdullah; Altuwaijri, Waleed; Alsahli, Saud; Aldhalaan, Hesham; Alkuraya, Fowzan S; Hundallah, Khalid; Mahmoud, Adel; Alasmari, Ali; Mutairi, Fuad Al; Abduraouf, Hanem; AlRasheed, Layan; Alshahwan, Saad; Tabarki, Brahim

    2017-10-01

    We retrospectively reviewed Saudi patients who had a congenital disorder of glycosylation (CDG). Twenty-seven Saudi patients (14 males, 13 females) from 13 unrelated families were identified. Based on molecular studies, the 27 CDG patients were classified into different subtypes: ALG9-CDG (8 patients, 29.5%), ALG3-CDG (7 patients, 26%), COG6-CDG (7 patients, 26%), MGAT2-CDG (3 patients, 11%), SLC35A2-CDG (1 patient), and PMM2-CDG (1 patient). All the patients had homozygous gene mutations. The combined carrier frequency of CDG for the encountered founder mutations in the Saudi population is 11.5 per 10,000, which translates to a minimum disease burden of 14 patients per 1,000,000. Our study provides comprehensive epidemiologic information and prevalence figures for each of these CDG in a large cohort of congenital disorder of glycosylation patients. © 2017 Wiley Periodicals, Inc.

  20. Optimal Synthetic Glycosylation of a Therapeutic Antibody.

    Science.gov (United States)

    Parsons, Thomas B; Struwe, Weston B; Gault, Joseph; Yamamoto, Keisuke; Taylor, Thomas A; Raj, Ritu; Wals, Kim; Mohammed, Shabaz; Robinson, Carol V; Benesch, Justin L P; Davis, Benjamin G

    2016-02-12

    Glycosylation patterns in antibodies critically determine biological and physical properties but their precise control is a significant challenge in biology and biotechnology. We describe herein the optimization of an endoglycosidase-catalyzed glycosylation of the best-selling biotherapeutic Herceptin, an anti-HER2 antibody. Precise MS analysis of the intact four-chain Ab heteromultimer reveals nonspecific, non-enzymatic reactions (glycation), which are not detected under standard denaturing conditions. This competing reaction, which has hitherto been underestimated as a source of side products, can now be minimized. Optimization allowed access to the purest natural form of Herceptin to date (≥90 %). Moreover, through the use of a small library of sugars containing non-natural functional groups, Ab variants containing defined numbers of selectively addressable chemical tags (reaction handles at Sia C1) in specific positions (for attachment of cargo molecules or "glycorandomization") were readily generated.

  1. Dengue Virus Glycosylation: What Do We Know?

    Directory of Open Access Journals (Sweden)

    Sally S. L. Yap

    2017-07-01

    Full Text Available In many infectious diseases caused by either viruses or bacteria, pathogen glycoproteins play important roles during the infection cycle, ranging from entry to successful intracellular replication and host immune evasion. Dengue is no exception. Dengue virus glycoproteins, envelope protein (E and non-structural protein 1 (NS1 are two popular sub-unit vaccine candidates. E protein on the virion surface is the major target of neutralizing antibodies. NS1 which is secreted during DENV infection has been shown to induce a variety of host responses through its binding to several host factors. However, despite their critical role in disease and protection, the glycosylated variants of these two proteins and their biological importance have remained understudied. In this review, we seek to provide a comprehensive summary of the current knowledge on protein glycosylation in DENV, and its role in virus biogenesis, host cell receptor interaction and disease pathogenesis.

  2. Composite magnetic nanoparticles: Synthesis and cancer-related applications

    International Nuclear Information System (INIS)

    Cai Ping; Chen Hong-Min; Xie Jin

    2014-01-01

    Recent advances in the preparation and applications of composite magnetic nanoparticles are reviewed and summarized, with a focus on cancer-related applications. (topical review - magnetism, magnetic materials, and interdisciplinary research)

  3. Glycosyl-Nucleolipids as new bioinspired amphiphiles.

    Science.gov (United States)

    Latxague, Laurent; Patwa, Amit; Amigues, Eric; Barthélémy, Philippe

    2013-09-30

    Four new Glycosyl-NucleoLipid (GNL) analogs featuring either a single fluorocarbon or double hydrocarbon chains were synthesized in good yields from azido thymidine as starting material. Physicochemical studies (surface tension measurements, differential scanning calorimetry) indicate that hydroxybutanamide-based GNLs feature endothermic phase transition temperatures like the previously reported double chain glycerol-based GNLs. The second generation of GNFs featuring a free nucleobase reported here presents a better surface activity (lower glim) compared to the first generation of GNFs.

  4. Relative Risks for Lethal Prostate Cancer Based on Complete Family History of Prostate Cancer Death.

    Science.gov (United States)

    Albright, Frederick S; Stephenson, Robert A; Agarwal, Neeraj; Cannon-Albright, Lisa A

    2017-01-01

    There are few published familial relative risks (RR) for lethal prostate cancer. This study estimates RRs for lethal prostate cancer based on comprehensive family history data, with the goal of improving identification of those men at highest risk of dying from prostate cancer. We used a population-based genealogical resource linked to a statewide electronic SEER cancer registry and death certificates to estimate relative risks (RR) for death from prostate cancer based upon family history. Over 600,000 male probands were analyzed, representing a variety of family history constellations of lethal prostate cancer. RR estimates were based on the ratio of the observed to the expected number of lethal prostate cancer cases using internal rates. RRs for lethal prostate cancer based on the number of affected first-degree relatives (FDR) ranged from 2.49 (95% CI: 2.27, 2.73) for exactly 1 FDR to 5.30 (2.13, 10.93) for ≥3 affected FDRs. In an absence of affected FDRs, increased risk was also significant for increasing numbers of affected second-degree or third degree relatives. Equivalent risks were observed for similar maternal and paternal family history. This study provides population-based estimates of lethal prostate cancer risk based on lethal prostate cancer family history. Many family history constellations associated with two to greater than five times increased risk for lethal prostate cancer were identified. These lethal prostate cancer risk estimates hold potential for use in identification, screening, early diagnosis, and treatment of men at high risk for death from prostate cancer. Prostate77:41-48, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. N-Glycosylation of cholera toxin B subunit: serendipity for novel plant-made vaccines?

    Directory of Open Access Journals (Sweden)

    Nobuyuki eMatoba

    2015-12-01

    Full Text Available The non-toxic B subunit of cholera toxin (CTB has attracted considerable interests from vaccinologists due to strong mucosal immunomodulatory effects and potential utility as a vaccine scaffold for heterologous antigens. Along with other conventional protein expression systems, various plant species have been used as recombinant production hosts for CTB and its fusion proteins. However, it has recently become clear that the protein is N-glycosylated within the endoplasmic reticulum of plant cells – a eukaryotic post-translational modification that is not present in native CTB. While functionally active aglycosylated variants have been successfully engineered to circumvent potential safety and regulatory issues related to glycosylation, this modification may actually provide advantageous characteristics to the protein as a vaccine platform. Based on data from our recent studies, I discuss the unique features of N-glycosylated CTB produced in plants for the development of novel vaccines.

  6. Carbohydrates on Proteins: Site-Specific Glycosylation Analysis by Mass Spectrometry

    Science.gov (United States)

    Zhu, Zhikai; Desaire, Heather

    2015-07-01

    Glycosylation on proteins adds complexity and versatility to these biologically vital macromolecules. To unveil the structure-function relationship of glycoproteins, glycopeptide-centric analysis using mass spectrometry (MS) has become a method of choice because the glycan is preserved on the glycosylation site and site-specific glycosylation profiles of proteins can be readily determined. However, glycopeptide analysis is still challenging given that glycopeptides are usually low in abundance and relatively difficult to detect and the resulting data require expertise to analyze. Viewing the urgent need to address these challenges, emerging methods and techniques are being developed with the goal of analyzing glycopeptides in a sensitive, comprehensive, and high-throughput manner. In this review, we discuss recent advances in glycoprotein and glycopeptide analysis, with topics covering sample preparation, analytical separation, MS and tandem MS techniques, as well as data interpretation and automation.

  7. Cancer incidence in relatives of British Fanconi Anaemia patients

    Directory of Open Access Journals (Sweden)

    Hodgson Shirley V

    2008-09-01

    Full Text Available Abstract Background Fanconi anemia (FA is an autosomal recessive DNA repair disorder with affected individuals having a high risk of developing acute myeloid leukaemia and certain solid tumours. Thirteen complementation groups have been identified and the genes for all of these are known (FANCA, B, C, D1/BRCA2, D2, E, F, G, I, J/BRIP1, L, M and N/PALB2. Previous studies of cancer incidence in relatives of Fanconi anemia cases have produced conflicting results. A study of British FA families was therefore carried out to investigate this question, since increases in cancer risk in FA heterozygotes would have implications for counselling FA family members, and possibly also for the implementation of preventative screening measures in FA heterozygotes. Methods Thirty-six families took part and data was collected on 575 individuals (276 males, 299 females, representing 18,136 person years. In this cohort, 25 males and 30 females were reported with cancer under the age of 85 years, and 36 cancers (65% could be confirmed from death certificates, cancer registries or clinical records. Results A total of 55 cancers were reported in the FA families compared to an estimated incidence of 56.95 in a comparable general population cohort, and the relative risk of cancer was 0.97 (95% C.I. = 0.71–1.23, p = 0.62 for FA family members. Analysis of relative risk for individual cancer types in each carrier probability group did not reveal any significant differences with the possible exception of prostate cancer (RR = 3.089 (95% C.I. = 1.09 – 8.78; Χ2 = 4.767, p = 0.029. Conclusion This study has not shown a significant difference in overall cancer risk in FA families.

  8. Risk of ovarian cancer in women with first-degree relatives with cancer

    DEFF Research Database (Denmark)

    Soegaard, Marie; Frederiksen, Kirsten; Jensen, Allan

    2009-01-01

    OBJECTIVE: To assess the risk of ovarian cancer in women with first-degree relatives with cancer at one of the four most frequent hereditary sites based on validated cancer diagnoses and to examine the association according to age at diagnosis of ovarian cancer and histology. DESIGN: Case......-control study. SETTING AND POPULATION: First-degree relatives of 554 women with invasive epithelial ovarian cancer and 1,564 controls were included. METHODS: Analyses were performed using multiple logistic regression models. RESULTS: Ovarian cancer in a first-degree relative was significantly associated...... with increased risk of ovarian cancer (OR, 2.4; 95% CI, 1.4-4.1 (mother or sister)). Ovarian cancer in a first-degree relative appeared to be a stronger risk factor for early-onset (cancer than late-onset (OR, 5.3; 95% CI, 2.0-14.1 vs. OR, 1.8; 95% CI, 1.0-3.4). The positive association...

  9. Relative quality of internet-derived gastrointestinal cancer information.

    Science.gov (United States)

    Chan, David S Y; Willicombe, Anita; Reid, Thomas D; Beaton, Ceri; Arnold, David; Ward, James; Davies, I Llion; Lewis, Wyn G

    2012-12-01

    Internet-derived health care information is increasingly accessed by patients, yet its quality and accuracy is variable and unregulated. The aim of this study was to assess the information available regarding common gastrointestinal cancers via three internet search engines (Google, Yahoo and Bing). The top 30 websites for each of the terms: oesophageal, gastric, pancreatic, colon and rectal cancer were evaluated (University of Michigan Consumer Health Website Checklist) and scored [-80 (poor) to 90 (excellent)]. The median score was 53 (-7 to 81) and was significantly higher for oesophageal (61) and pancreatic (65) cancer websites, compared with gastric (49), colon (48) and rectal cancer (50) (p = 0.014). Median scores related to charitable organisations were significantly better than academic, commercial, news agency, care provider, layperson and medical information websites collectively (79 vs. 42, p < 0.0001). Overall quality of internet-derived gastrointestinal cancer information remains poor and patients and clinicians should be aware.

  10. [Cancer and family: tasks and stress of relatives].

    Science.gov (United States)

    Popek, V; Hönig, K

    2015-03-01

    Relatives are the primary and existential resource of cancer patients, while at the same time experiencing substantial distress themselves. This article presents a description of tasks, roles and distress factors, the prevalence of psychosocial distress, description of risk factors in families contributing to dysfunctional coping, options and empirical evidence for the efficacy of psychosocial support. Evaluation of registry data, analysis of case reports, discussion of basic research findings, meta-analyses and expert judgments. Psychosocial distress in relatives of cancer patients is comparable to the degree of distress experienced by the patients and is sometimes even higher. Distress in relatives is still underrecognized, underreported and undertreated. Hostile interaction patterns, low emotional expression and high conflict tendencies impair coping with cancer and its treatment. Psychosocial support for the family of cancer patients improves coping behavior and the quality of life both in relatives and patients. Professional and lay caregivers need to adopt a social perspective on cancer whereby participation and inclusion of relatives in the treatment, acknowledgment of their engagement and recognition of their distress is beneficial for both patients and their relatives. Screening for psychosocial distress in relatives is recommended, attention should be drawn to psychosocial support services and utilization should be encouraged.

  11. Host pathogen interactions in Helicobacter pylori related gastric cancer

    Science.gov (United States)

    Chmiela, Magdalena; Karwowska, Zuzanna; Gonciarz, Weronika; Allushi, Bujana; Stączek, Paweł

    2017-01-01

    Helicobacter pylori (H. pylori), discovered in 1982, is a microaerophilic, spiral-shaped gram-negative bacterium that is able to colonize the human stomach. Nearly half of the world's population is infected by this pathogen. Its ability to induce gastritis, peptic ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma has been confirmed. The susceptibility of an individual to these clinical outcomes is multifactorial and depends on H. pylori virulence, environmental factors, the genetic susceptibility of the host and the reactivity of the host immune system. Despite the host immune response, H. pylori infection can be difficult to eradicate. H. pylori is categorized as a group I carcinogen since this bacterium is responsible for the highest rate of cancer-related deaths worldwide. Early detection of cancer can be lifesaving. The 5-year survival rate for gastric cancer patients diagnosed in the early stages is nearly 90%. Gastric cancer is asymptomatic in the early stages but always progresses over time and begins to cause symptoms when untreated. In 97% of stomach cancer cases, cancer cells metastasize to other organs. H. pylori infection is responsible for nearly 60% of the intestinal-type gastric cancer cases but also influences the development of diffuse gastric cancer. The host genetic susceptibility depends on polymorphisms of genes involved in H. pylori-related inflammation and the cytokine response of gastric epithelial and immune cells. H. pylori strains differ in their ability to induce a deleterious inflammatory response. H. pylori-driven cytokines accelerate the inflammatory response and promote malignancy. Chronic H. pylori infection induces genetic instability in gastric epithelial cells and affects the DNA damage repair systems. Therefore, H. pylori infection should always be considered a pro-cancerous factor. PMID:28321154

  12. Halide-mediated regioselective 6-O-glycosylation of unprotected hexopyranosides with perbenzylated glycosyl bromide donors

    DEFF Research Database (Denmark)

    Niedbal, Dominika Alina; Madsen, Robert

    2016-01-01

    The regio- and stereoselective glycosylation at the 6-position in 2,3,4,6-unprotected hexopyranosides has been investigated with dibutyltin oxide as the directing agent. Perbenzylated hexopyranosyl bromides were employed as the donors and the glycosylations were promoted by tetrabutylammonium...... bromide. The couplings were completely selective for both glucose and galactose donors and acceptors as long as the stannylene acetal of the acceptor was soluble in dichloromethane. This gave rise to a number of 1,2-cis-linked disaccharides in reasonable yields. Mannose donors and acceptors, on the other...

  13. Oxycodone for cancer-related pain.

    Science.gov (United States)

    Schmidt-Hansen, Mia; Bennett, Michael I; Arnold, Stephanie; Bromham, Nathan; Hilgart, Jennifer S

    2015-02-27

    Many patients with cancer experience moderate to severe pain that requires treatment with strong opioids, of which oxycodone and morphine are examples. Strong opioids are, however, not effective for pain in all patients, nor are they well-tolerated by all patients. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for patients with cancer pain. To assess the effectiveness and tolerability of oxycodone for pain in adults with cancer. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), EMBASE (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), PsycINFO (Ovid) and PubMed to March 2014. We also searched Clinicaltrials.gov, metaRegister of Controlled Trials (mRCT), EU Clinical Trials Register and World Health Organization International Clinical Trials Registry Platform (ICTRP). We checked the bibliographic references of relevant identified studies and contacted the authors of the included studies to find additional trials not identified by the electronic searches. No language, date or publication status restrictions were applied to the search. We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults. Two authors independently extracted study data (study design, participant details, interventions and outcomes) and independently assessed the quality of the included studies according to standard Cochrane methodology. Where possible, we meta-analysed the pain intensity data using the generic inverse variance method, otherwise these data were summarised narratively along with the adverse event and patient preference data. The overall quality of the evidence for each outcome

  14. Glycosylation in HIV-1 envelope glycoprotein and its biological implications

    KAUST Repository

    Ho, Yung Shwen

    2013-08-01

    Glycosylation of HIV-1 envelope proteins (Env gp120/gp41) plays a vital role in viral evasion from the host immune response, which occurs through the masking of key neutralization epitopes and the presentation of the Env glycosylation as \\'self\\' to the host immune system. Env glycosylation is generally conserved, yet its continual evolution plays an important role in modulating viral infectivity and Env immunogenicity. Thus, it is believed that Env glycosylation, which is a vital part of the HIV-1 architecture, also controls intra- and inter-clade genetic variations. Discerning intra- and inter-clade glycosylation variations could therefore yield important information for understanding the molecular and biological differences between HIV clades and may assist in effectively designing Env-based immunogens and in clearly understanding HIV vaccines. This review provides an in-depth perspective of various aspects of Env glycosylation in the context of HIV-1 pathogenesis. © 2013 Future Medicine Ltd.

  15. Factors related to treatment refusal in Taiwanese cancer patients.

    Science.gov (United States)

    Chiang, Ting-Yu; Wang, Chao-Hui; Lin, Yu-Fen; Chou, Shu-Lan; Wang, Ching-Ting; Juang, Hsiao-Ting; Lin, Yung-Chang; Lin, Mei-Hsiang

    2015-01-01

    Incidence and mortality rates for cancer have increased dramatically in the recent 30 years in Taiwan. However, not all patients receive treatment. Treatment refusal might impair patient survival and life quality. In order to improve this situation, we proposed this study to evaluate factors that are related to refusal of treatment in cancer patients via a cancer case manager system. This study analysed data from a case management system during the period from 2010 to 2012 at a medical center in Northern Taiwan. We enrolled a total of 14,974 patients who were diagnosed with cancer. Using the PRECEDE Model as a framework, we conducted logistic regression analysis to identify independent variables that are significantly associated with refusal of therapy in cancer patients. A multivariate logistic regression model was also applied to estimate adjusted the odds ratios (ORs) with 95% confidence intervals (95%CI). A total of 253 patients (1.69%) refused treatment. The multivariate logistic regression result showed that the high risk factors for refusal of treatment in cancer patient included: concerns about adverse effects (prefuse treatment have poor survival. The present study provides evidence of factors that are related to refusal of therapy and might be helpful for further application and improvement of cancer care.

  16. XMRV Discovery and Prostate Cancer-Related Research

    Directory of Open Access Journals (Sweden)

    David E. Kang

    2011-01-01

    Full Text Available Xenotropic murine leukemia virus-related virus (XMRV was first reported in 2006 in a study of human prostate cancer patients with genetic variants of the antiviral enzyme, RNase L. Subsequent investigations in North America, Europe, Asia, and Africa have either observed or failed to detect XMRV in patients (prostate cancer, chronic fatigue syndrome-myalgic encephalomyelitis (CFS-ME, and immunosuppressed with respiratory tract infections or normal, healthy, control individuals. The principal confounding factors are the near ubiquitous presence of mouse-derived reagents, antibodies and cells, and often XMRV itself, in laboratories. XMRV infects and replicates well in many human cell lines, but especially in certain prostate cancer cell lines. XMRV also traffics to prostate in a nonhuman primate model of infection. Here, we will review the discovery of XMRV and then focus on prostate cancer-related research involving this intriguing virus.

  17. Neuronal glycosylation differentials in normal, injured and chondroitinase-treated environments

    International Nuclear Information System (INIS)

    Kilcoyne, Michelle; Sharma, Shashank; McDevitt, Niamh; O’Leary, Claire; Joshi, Lokesh; McMahon, Siobhán S.

    2012-01-01

    Highlights: ► Carbohydrates are important in the CNS and ChABC has been used for spinal cord injury (SCI) treatment. ► Neuronal glycosylation in injury and after ChABC treatment is unknown. ► In silico mining verified that glyco-related genes were differentially regulated after SCI. ► In vitro model system revealed abnormal sialylation in an injured environment. ► The model indicated a return to normal neuronal glycosylation after ChABC treatment. -- Abstract: Glycosylation is found ubiquitously throughout the central nervous system (CNS). Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily substituted with glycosaminoglycans (GAGs) and are found in the extracellular matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial scar, including NG2, and these CSPGs are key inhibitory molecules of axonal regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the inhibitory nature of NG2. A gene expression dataset was mined in silico to verify differentially regulated glycosylation-related genes in neurons after spinal cord injury and identify potential targets for further investigation. To establish the glycosylation differential of neurons that grow in a healthy, inhibitory and ChABC-treated environment, we established an indirect co-culture system where PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days culture, lectin cytochemistry of the neurons was performed using five fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually α-(2,6)-linked sialylation scarcely occurs in the CNS but this motif was observed on the neurons in the injured environment only at day 8. Treatment with ChABC was successful in returning neuronal glycosylation to normal conditions at all timepoints for MAA, PNA and SNA-I staining

  18. Neuronal glycosylation differentials in normal, injured and chondroitinase-treated environments

    Energy Technology Data Exchange (ETDEWEB)

    Kilcoyne, Michelle; Sharma, Shashank [Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland, Galway (Ireland); McDevitt, Niamh; O' Leary, Claire [Anatomy, School of Medicine, National University of Ireland, Galway (Ireland); Joshi, Lokesh [Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland, Galway (Ireland); McMahon, Siobhan S., E-mail: siobhan.mcmahon@nuigalway.ie [Anatomy, School of Medicine, National University of Ireland, Galway (Ireland)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer Carbohydrates are important in the CNS and ChABC has been used for spinal cord injury (SCI) treatment. Black-Right-Pointing-Pointer Neuronal glycosylation in injury and after ChABC treatment is unknown. Black-Right-Pointing-Pointer In silico mining verified that glyco-related genes were differentially regulated after SCI. Black-Right-Pointing-Pointer In vitro model system revealed abnormal sialylation in an injured environment. Black-Right-Pointing-Pointer The model indicated a return to normal neuronal glycosylation after ChABC treatment. -- Abstract: Glycosylation is found ubiquitously throughout the central nervous system (CNS). Chondroitin sulphate proteoglycans (CSPGs) are a group of molecules heavily substituted with glycosaminoglycans (GAGs) and are found in the extracellular matrix (ECM) and cell surfaces. Upon CNS injury, a glial scar is formed, which is inhibitory for axon regeneration. Several CSPGs are up-regulated within the glial scar, including NG2, and these CSPGs are key inhibitory molecules of axonal regeneration. Treatment with chondroitinase ABC (ChABC) can neutralise the inhibitory nature of NG2. A gene expression dataset was mined in silico to verify differentially regulated glycosylation-related genes in neurons after spinal cord injury and identify potential targets for further investigation. To establish the glycosylation differential of neurons that grow in a healthy, inhibitory and ChABC-treated environment, we established an indirect co-culture system where PC12 neurons were grown with primary astrocytes, Neu7 astrocytes (which overexpress NG2) and Neu7 astrocytes treated with ChABC. After 1, 4 and 8 days culture, lectin cytochemistry of the neurons was performed using five fluorescently-labelled lectins (ECA MAA, PNA, SNA-I and WFA). Usually {alpha}-(2,6)-linked sialylation scarcely occurs in the CNS but this motif was observed on the neurons in the injured environment only at day 8. Treatment

  19. Improvements in 5-year outcomes of stage II/III rectal cancer relative to colon cancer.

    Science.gov (United States)

    Renouf, Daniel J; Woods, Ryan; Speers, Caroline; Hay, John; Phang, P Terry; Fitzgerald, Catherine; Kennecke, Hagen

    2013-12-01

    Stage for stage, rectal cancer has historically been associated with inferior survival compared with colon cancer. Randomized trials of rectal cancer have generally demonstrated improvements in locoregional relapse but not survival. We compared therapy and outcomes of colon versus rectal cancer in 2 time cohorts to determine if relative improvements have occurred. Patients with resected stage II/III colorectal cancer referred to the British Columbia Cancer Agency in 1989/1990 and 2001/2002 were identified. The higher of clinical or pathologic stage was used for patients receiving preoperative chemoradiation. Disease-specific survival (DSS) and overall survival (OS) were compared for rectal and colon cancer between the 2 cohorts. Kaplan-Meier method was used for survival analysis. A total of 1427 patients were included, with 375 from 1989/1990 and 1052 from 2001/2002. Between 1989/1990 and 2001/2002 there were significant increases in the use of perioperative chemotherapy for both rectal and colon cancer (Prectal cancer. DSS significantly improved for rectal (Pcolon cancer (P=0.069). Five-year OS was significantly inferior for rectal versus colon cancer in 1989/1990 (46.1% vs. 57.2%, P=0.023) and was similar to that of colon cancer in 2001/2002 (63.7% vs. 66.2%, P=0.454). Advances in locoregional and systemic therapy significantly improved survival among patients with rectal cancer. DSS and OS are now similar between colon and rectal cancer for both stage II and III disease.

  20. Links between CD147 Function, Glycosylation, and Caveolin-1

    OpenAIRE

    Tang, Wei; Chang, Sharon B.; Hemler, Martin E.

    2004-01-01

    Cell surface CD147 shows remarkable variations in size (31-65 kDa) because of heterogeneous N-glycosylation, with the most highly glycosylated forms functioning to induce matrix metalloproteinase (MMP) production. Here we show that all three CD147 N-glycosylation sites make similar contributions to both high and low glycoforms (HG- and LG-CD147). l-Phytohemagglutinin lectin binding and swainsonine inhibition experiments indicated that HG-CD147 contains N-acetylglucosaminyltransferase V-cataly...

  1. How new subscribers use cancer-related online mailing lists.

    Science.gov (United States)

    Rimer, Barbara K; Lyons, Elizabeth J; Ribisl, Kurt M; Bowling, J Michael; Golin, Carol E; Forlenza, Michael J; Meier, Andrea

    2005-07-01

    Online cancer-related support is an under-studied resource that may serve an important function in the information seeking, care, and support of cancer patients and their families. With over 9.8 million cancer survivors (defined as anyone living with cancer) in the United States alone and the number growing worldwide, it is important to understand how they seek and use online resources to obtain the information they need, when they need it, and in a form and manner appropriate to them. These are stated cancer communication goals of the US National Cancer Institute. Our purposes are to (1) present background information about online mailing lists and electronic support groups, (2) describe the rationale and methodology for the Health eCommunities (HeC) study, and (3) present preliminary baseline data on new subscribers to cancer-related mailing lists. In particular, we describe subscribers' use of mailing lists, their reasons for using them, and their reactions to participating shortly after joining the lists. From April to August 2004, we invited all new subscribers to 10 Association of Cancer Online Resources mailing lists to complete Web-based surveys. We analyzed baseline data from the respondents to examine their perceptions about cancer-related mailing lists and to describe how cancer patients and survivors used these lists in the period shortly after joining them. Cumulative email invitations were sent to 1368 new mailing list subscribers; 293 Web surveys were completed within the allotted time frame (21.4% response rate). Most respondents were over age 50 (n = 203, 72%), white (n = 286, 98%), college graduates (n = 161, 55%), and had health insurance (n = 283, 97%). About 41% (n = 116) of new subscribers reported spending 1 to 3 hours per day reading and responding to list messages. They used the mailing lists for several reasons. Among the most frequently reported, 62% (n = 179) strongly agreed they used mailing lists to obtain information on how to deal

  2. Relation between nitrate and nitrite food habits with lung cancer.

    Science.gov (United States)

    Karimzadeh, Laleh; Koohdani, Fariba; Siassi, Fereydoon; Mahmoudi, Mahmoud; Moslemi, Daryoush; Safari, Farid

    2012-01-01

    Nitrites, a probable human carcinogen, generate reactive nitrogen species that may cause damage to the lung. We evaluated the association between nutritional habits related to nitrite and nitrate intake and risk of lung cancer in Mazandaran, Northern Province of Iran. In this case-control study the two groups were matched for gender and age (+/- 5 years). A semi -quantitative food frequency questionnaire (FFQ) was used to collect dietary data about nutritional habits related to nitrate, nitrite, vitamins E and C intake, from 40 lung cancer cases and 40 control subjects admitted at Mazanaran hospitals. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of lung cancer using logistic regression. Mean score of nutritional habits in case group was significantly lower than that in control group (P less than or equal 0.001). We observed a positive association between animal sources of nitrate and nitrite intake (OR = 2.7, 95% CI: 0.13-0.96) and risk of lung cancer. Decreased risk of lung cancer was also observed with fruit intake (OR = 0.26, 95% CI: 1.3-11). Our results indicate a probable association between nutritional habits related to animal sources of nitrate and nitrite intake and the risk of lung cancer that requires to be confirmed by other studies.

  3. The glycosylated IgII extracellular domain of EMMPRIN is implicated in the induction of MMP-2.

    Science.gov (United States)

    Papadimitropoulou, Adriana; Mamalaki, Avgi

    2013-07-01

    EMMPRIN is a widely expressed transmembrane glycoprotein that plays important roles in many physiological and pathological processes, such as tumor invasion and metastasis. It stimulates the production of matrix metalloproteinase (MMPs) by tumor-associated fibroblasts. In the present study, our aim was to (a) to investigate if the IgII loop domain of the extracellular domain (ECD) of EMMPRIN contributes to the MMP production by fibroblasts and (b) to evaluate the significance of glycosylation in this process. For this purpose, we expressed the ECD, IgI, or IgII domains of EMMPRIN, in their glycosylated and non-glycosylated forms, in the heterologous expression systems of P. pastoris and E. coli, respectively. Dermal fibroblasts were treated with purified recombinant domains and proteins from cell extracts and supernatants were analyzed by Western blot and zymography assays. Fibroblasts treated with ECD-, IgI-, and IgII-glycosylated domains of EMMPRIN significantly stimulated the gelatinolytic activity of MMP-2, compared to untreated fibroblasts, whereas no significant effect was observed after treatment with the non-glycosylated ECD, IgI, and IgII domains. Western blot analysis from cell extracts and supernatants revealed that only the glycosylated forms were able to stimulate MMP-2 production and secretion, respectively. Quantitative PCR revealed that this effect was not attributed to transcriptional alterations. This study showed that N-glycosylation was a prerequisite for efficient MMP-2 production, with the IgII loop domain contributing significantly to this process. Perturbation of the function of IgII-EMMPRIN loop could have potential therapeutic value in the inhibition of MMP-2-dependent cancer cell invasion and metastasis.

  4. Relationship between cancer-related fatigue and physical activity in inpatient cancer rehabilitation.

    Science.gov (United States)

    Kummer, Franziska; Catuogno, Silvio; Perseus, Josef M; Bloch, Wilhelm; Baumann, Freerk T

    2013-08-01

    Fatigue is a serious problem for the majority of patients with cancer. In this context, several studies have shown benefits of physical activity during and following treatment. However, uncertainties remain regarding the optimal type and duration of physical activity. Therefore, this study examined the relationship between cancer-related fatigue and physical activity in the course of inpatient rehabilitation. Fatigue (Multidimensional Fatigue Inventory) and physical activity (Freiburg Questionnaire of Physical Activity) were assessed in a consecutive series of 35 patients with cancer attending oncological inpatient rehabilitation during a six-month study period. The three-week rehabilitation program included daily exercise therapy consisting of aerobic endurance training, moderate resistance training, coordination exercises, relaxation training and individual physiotherapy. At discharge, a significant improvement in each dimension of cancer-related fatigue (p=0.001-0.003) and a significant increase of physical activity levels (p=0.001) were observed. A small, but significant negative correlation was found between cancer-related fatigue and the level of physical activity (R=-0.438, p=0.004). The largest effects were associated with a weekly energy expenditure of 3000 kcal through physical activity. The results support a non-linear dose-response relationship between cancer-related fatigue and physical activity. Since this is the first study providing specific exercise recommendations for an effective treatment of cancer-related fatigue in the context of inpatient rehabilitation, further research is required to validate the observed trends.

  5. Is glycosylated haemoglobin a marker of fertility?

    DEFF Research Database (Denmark)

    Hjollund, N H; Jensen, T K; Bonde, J P

    1999-01-01

    We performed a follow-up study of time to pregnancy in a population of first-time pregnancy planners without previous reproductive experience. The objective of this paper is to report and discuss a finding of a strong relationship between glycosylated haemoglobin (HbA1C) and fertility. A total...... concentration of inhibin A. No association was found between HbA1C and psychosocial distress. The reduced fertility among women with high HbA1C may be due to an association with subclinical polycystic ovaries as indicated by the hormonal profile....

  6. Glycosyl-Nucleolipids as New Bioinspired Amphiphiles

    Directory of Open Access Journals (Sweden)

    Philippe Barthélémy

    2013-09-01

    Full Text Available Four new Glycosyl-NucleoLipid (GNL analogs featuring either a single fluorocarbon or double hydrocarbon chains were synthesized in good yields from azido thymidine as starting material. Physicochemical studies (surface tension measurements, differential scanning calorimetry indicate that hydroxybutanamide-based GNLs feature endothermic phase transition temperatures like the previously reported double chain glycerol-based GNLs. The second generation of GNFs featuring a free nucleobase reported here presents a better surface activity (lower glim compared to the first generation of GNFs.

  7. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability.

    Science.gov (United States)

    Colotta, Francesco; Allavena, Paola; Sica, Antonio; Garlanda, Cecilia; Mantovani, Alberto

    2009-07-01

    Inflammatory conditions in selected organs increase the risk of cancer. An inflammatory component is present also in the microenvironment of tumors that are not epidemiologically related to inflammation. Recent studies have begun to unravel molecular pathways linking inflammation and cancer. In the tumor microenvironment, smoldering inflammation contributes to proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, reduced response to hormones and chemotherapeutic agents. Recent data suggest that an additional mechanism involved in cancer-related inflammation (CRI) is induction of genetic instability by inflammatory mediators, leading to accumulation of random genetic alterations in cancer cells. In a seminal contribution, Hanahan and Weinberg [(2000) Cell, 100, 57-70] identified the six hallmarks of cancer. We surmise that CRI represents the seventh hallmark.

  8. Effects of an expressive writing intervention on cancer-related distress in Danish breast cancer survivors

    DEFF Research Database (Denmark)

    Jensen-Johansen, Mikael Birkelund; Christensen, Søren; Valdimarsdottir, Heiddis

    2013-01-01

    Objective: To examine the effects of an expressive writing intervention (EWI) on cancer-related distress, depressive symptoms, and mood in women treated for early stage breast cancer. Methods: A nationwide sample of 507 Danish women who had recently completed treatment for primary breast cancer...... were randomly assigned to three 20-min home-based writing exercises, one week apart, focusing on either emotional disclosure (EWI group) or a non-emotional topic (control group). Cancer-related distress [Impact of Event Scale (IES)], depressive symptoms (Beck Depression Inventory—Short Form......), and negative (37-item Profile of Moods State) and positive mood (Passive Positive Mood Scale) were assessed at baseline and at 3 and 9 months post-intervention. Choice of writing topic (cancer versus other), alexithymia (20-item Toronto Alexithymia Scale), and social constraints (Social Constraints Scale) were...

  9. Resilience and positive affect contribute to lower cancer-related fatigue among Chinese patients with gastric cancer.

    Science.gov (United States)

    Zou, Guiyuan; Li, Ye; Xu, Ruicai; Li, Ping

    2018-04-01

    To investigate the prevalence of cancer-related fatigue and explore the relationship between resilience, positive affect, and fatigue among Chinese patients with gastric cancer. Cancer-related fatigue is the most distressing symptom reported frequently by cancer patients during both treatment and survival phases. Resilience and positive affect as vital protective factors against cancer-related fatigue have been examined, but the underlying psychological mechanisms are not well understood. A cross-sectional study. Two hundred and three gastric cancer patients were enrolled from three hospitals in China. The Cancer Fatigue Scale, the positive affect subscale of the Positive and Negative Affect Schedule and the Connor-Davidson Resilience Scale (CD-RISC10) were administered. Hierarchical linear regression modelling was conducted to examine the association between resilience and cancer-related fatigue, and the mediating effect of positive affect. The incidence of clinically relevant fatigue among patients with gastric cancer was 91.6%. Regression analysis showed that resilience was negatively associated with cancer-related fatigue, explaining 15.4% of variance in cancer-related fatigue. Mediation analysis showed that high resilience was associated with increased positive affect, which was associated with decreased cancer-related fatigue. Cancer-related fatigue is prevalent among patients with gastric cancer. Positive affect may mediate the relationship between resilience and cancer-related fatigue. Interventions that attend to resilience training and promotion of positive affect may be the focus for future clinical and research endeavours. © 2017 John Wiley & Sons Ltd.

  10. How are cancer and connective tissue diseases related to sarcoidosis?

    Science.gov (United States)

    Chopra, Amit; Judson, Marc A

    2015-09-01

    Several studies have suggested an association between sarcoidosis and cancer, and between sarcoidosis and connective tissue diseases (CTDs). In this review, we discuss the evidence supporting and refuting these associations. In terms of a cancer risk in sarcoidosis patients, the data are somewhat conflicting but generally show a very small increased risk. The data supporting an association between sarcoidosis and CTD are not as robust as for cancer. However, it appears that scleroderma is the CTD most strongly associated with sarcoidosis. There are several important clinical and research-related implications of the association of sarcoidosis and CTDs. First, rigorous efforts should be made to exclude alternative causes for granulomatous inflammation before establishing a diagnosis of sarcoidosis. Second, the association between sarcoidosis and both cancer and CTDs may yield important insights into the immunopathogenesis of all three diseases. Finally, these data provide insight in answering a common question asked by sarcoidosis patients, 'Am I at an increased risk of developing cancer?' We believe that although there is an increased (relative) risk of cancer in sarcoidosis patients compared with the general population, that increased risk is quite small (low absolute risk).

  11. Ovarian cancer-related hypophosphatemic osteomalacia--a case report.

    Science.gov (United States)

    Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao; Tsai, Keh-Sung

    2014-12-01

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. We investigated a 57-year-old woman with progressive low back pain. Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia.

  12. Ovarian Cancer-Related Hypophosphatemic Osteomalacia—A Case Report

    Science.gov (United States)

    Lin, Hung-An; Shih, Shyang-Rong; Tseng, Yu-Ting; Chen, Chi-Hau; Chiu, Wei-Yih; Hsu, Chih-Yao

    2014-01-01

    Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused primarily by benign mesenchymal tumors. It has been associated with malignancies in rare cases. High serum levels of fibroblast growth factor (FGF) 23 reported in a group of patients with ovarian cancer had normal serum phosphate levels. There had been no ovarian cancer-related hypophosphatemic osteomalacia in a search of the literature. Objective: We investigated a 57-year-old woman with progressive low back pain. Design and Intervention: Clinical, biochemical, and radiological assessments were performed. The patient's serum phosphate and FGF23 levels were evaluated at baseline and after treatment for ovarian cancer. Results: The patient presented with progressive low back pain and weight loss during the previous 6 months. Imaging studies revealed low bone mineral density and multiple suspicious spinal metastatic lesions. Laboratory examination showed hypophosphatemia, hyperphosphaturia, normocalcemia, an elevated serum alkaline phosphatase level, and an elevated serum FGF23 level. Because TIO was suspected, a tumor survey was performed, and ovarian carcinoma with multiple metastasis was detected. After surgery and chemotherapy treatments for ovarian cancer, the serum phosphate and FGF23 levels returned to normal, and the low back pain improved. Conclusions: To our knowledge, this is the first case of ovarian cancer-related hypophosphatemic osteomalacia reported in the literature. TIO should be considered in patients with ovarian cancer presenting with weakness, bone pain, and fractures. Investigation of TIO is appropriate when these patients present hypophosphatemia. PMID:25181387

  13. Cancer-related fatigue and physical activity among premenopausal cervical and endometrial cancer survivors in Japan

    OpenAIRE

    小濵, 京子; 丸, 光惠; 前田, 留美; 久保田, 俊郎

    2015-01-01

    Purpose: To examine the relationship between cancer-related fatigue (CRF) and physical activity in daily living in premenopausal disease-free cervical and endometrial cancer survivors. Methods: A physical activity monitor was used to collect objective data on daily physical activity. CRF and related variables were measured using self-report scales in a cross-sectional manner. Results: The average age was 44.9 years among 64 women. The higher CRF group comprised 22 women (34%), 10% of whom had...

  14. Evidence of peripheral nerve blocks for cancer-related pain

    DEFF Research Database (Denmark)

    Klepstad, P; Kurita, G P; Mercadante, S

    2015-01-01

    The European Association for Palliative Care has initiated a comprehensive program to achieve an over-all review of the evidence of multiple cancer pain management strategies in order to extend the current guideline for treatment of cancer pain. The present systematic review analyzed the existing...... evidence of analgesic efficacy for peripheral nerve blocks in adult patients with cancer. A search strategy was elaborated with words related to cancer, pain, peripheral nerve and block. The search was performed in PubMed, EMBASE, and Cochrane for the period until February 2014. The number of abstracts...... retrieved was 155. No controlled studies were identified. Sixteen papers presented a total of 79 cases. The blocks applied were paravertebral blocks (10 cases), blocks in the head region (2 cases), plexus blocks (13 cases), intercostal blocks (43 cases) and others (11 cases). In general, most cases reported...

  15. Intolerance of uncertainty, cognitive complaints, and cancer-related distress in prostate cancer survivors.

    Science.gov (United States)

    Eisenberg, Stacy A; Kurita, Keiko; Taylor-Ford, Megan; Agus, David B; Gross, Mitchell E; Meyerowitz, Beth E

    2015-02-01

    Prostate cancer survivors have reported cognitive complaints following treatment, and these difficulties may be associated with survivors' ongoing cancer-related distress. Intolerance of uncertainty may exacerbate this hypothesized relationship by predisposing individuals to approach uncertain situations such as cancer survivorship in an inflexible and negative manner. We investigated whether greater cognitive complaints and higher intolerance of uncertainty would interact in their relation to more cancer-related distress symptoms. This cross-sectional, questionnaire-based study included 67 prostate cancer survivors who were 3 to 5 years post treatment. Hierarchical multiple regression analyses tested the extent to which intolerance of uncertainty, cognitive complaints, and their interaction were associated with cancer-related distress (measured with the Impact of Event Scale-Revised; IES-R) after adjusting for age, education, physical symptoms, and fear of cancer recurrence. Intolerance of uncertainty was positively associated with the IES-R avoidance and hyperarousal subscales. More cognitive complaints were associated with higher scores on the IES-R hyperarousal subscale. The interaction of intolerance of uncertainty and cognitive complaints was significantly associated with IES-R intrusion, such that greater cognitive complaints were associated with greater intrusive thoughts in survivors high in intolerance of uncertainty but not those low in it. Prostate cancer survivors who report cognitive difficulties or who find uncertainty uncomfortable and unacceptable may be at greater risk for cancer-related distress, even 3 to 5 years after completing treatment. It may be beneficial to address both cognitive complaints and intolerance of uncertainty in psychosocial interventions. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Cancer-related identity and positive affect in survivors of prostate cancer.

    Science.gov (United States)

    Bellizzi, Keith M; Blank, Thomas O

    2007-03-01

    Despite a shift in the cancer culture and language used to describe individuals diagnosed with this disease, the extent to which individuals with cancer adopt a particular cancer-related identity and the impact of these identities in relation to their well-being is virtually unknown. Using a cross-sectional study design and a metropolitan tumor registry, a mail questionnaire to examine post-treatment quality of life was sent to prostate cancer (PCa) survivors. The sample consisted of 490 PCa survivors, ranging in age from 49-88 (M = 69.7; SD = 7.8), one to eight years after diagnosis. The outcome measure used in these analyses was the PANAS to assess positive and negative affect. The most frequently reported cancer-related identity was "someone who has had PCa" (57%). The least reported self view was "victim" (1%). Twenty-six percent of men self-identified as "survivors" while 6% thought of themselves as "cancer conquerors." Only 9% self-identified as a "patient." Multivariate analyses, adjusted for potential confounders, show respondents who identified themselves as "survivors" or "cancer conquerors" reported significantly higher scores on positive affect than men who self-identified as "patients" (p < .001). Although the majority of respondents identified themselves as "someone who has had cancer," identifying as a "survivor" or "someone who has conquered cancer" appears to have adaptive value for positive mood. Those who perceive themselves as survivors of prostate cancer may derive some benefit in well-being associated with this self assessment.

  17. Expression of Iron-Related Proteins Differentiate Non-Cancerous and Cancerous Breast Tumors

    Directory of Open Access Journals (Sweden)

    Sara Pizzamiglio

    2017-02-01

    Full Text Available We have previously reported hepcidin and ferritin increases in the plasma of breast cancer patients, but not in patients with benign breast disease. We hypothesized that these differences in systemic iron homeostasis may reflect alterations in different iron-related proteins also play a key biochemical and regulatory role in breast cancer. Thus, here we explored the expression of a bundle of molecules involved in both iron homeostasis and tumorigenesis in tissue samples. Enzyme-linked immunosorbent assay (ELISA or reverse-phase protein array (RPPA, were used to measure the expression of 20 proteins linked to iron processes in 24 non-cancerous, and 56 cancerous, breast tumors. We found that cancerous tissues had higher level of hepcidin than benign lesions (p = 0.012. The univariate analysis of RPPA data highlighted the following seven proteins differentially expressed between non-cancerous and cancerous breast tissue: signal transducer and transcriptional activator 5 (STAT5, signal transducer and activator of transcription 3 (STAT3, bone morphogenetic protein 6 (BMP6, cluster of differentiation 74 (CD74, transferrin receptor (TFRC, inhibin alpha (INHA, and STAT5_pY694. These findings were confirmed for STAT5, STAT3, BMP6, CD74 and INHA when adjusting for age. The multivariate statistical analysis indicated an iron-related 10-protein panel effective in separating non-cancerous from cancerous lesions including STAT5, STAT5_pY694, myeloid differentiation factor 88 (MYD88, CD74, iron exporter ferroportin (FPN, high mobility group box 1 (HMGB1, STAT3_pS727, TFRC, ferritin heavy chain (FTH, and ferritin light chain (FTL. Our results showed an association between some iron-related proteins and the type of tumor tissue, which may provide insight in strategies for using iron chelators to treat breast cancer.

  18. Location, location, location: new insights into O-GalNAc protein glycosylation

    DEFF Research Database (Denmark)

    Gill, David J; Clausen, Henrik; Bard, Frederic

    2011-01-01

    O-GalNAc glycosylation of proteins confers essential structural, protective and signaling roles in eumetazoans. Addition of O-glycans onto proteins is an extremely complex process that regulates both sites of attachment and the types of oligosaccharides added. Twenty distinct polypeptide GalNAc......-transferases (GalNAc-Ts) initiate O-glycosylation and fine-tuning their expression provides a mechanism for regulating this action. Recently, a new mode of regulation has emerged where activation of Src kinase selectively redistributes Golgi-localized GalNAc-Ts to the ER. This relocalization results in a strong...... increase in the density of O-glycan decoration. In this review, we discuss how different mechanisms can regulate the number and the types of O-glycans decorating proteins. In addition, we speculate how Src-dependent relocation of GalNAc-Ts could play an important role in cancerous cellular transformation....

  19. Soluble extracellular matrix metalloproteinase inducer (EMMPRIN, EMN) regulates cancer-related cellular functions by homotypic interactions with surface CD147.

    Science.gov (United States)

    Knutti, Nadine; Kuepper, Michael; Friedrich, Karlheinz

    2015-11-01

    EMMPRIN (extracellular matrix metalloproteinase inducer) is a widely expressed glycoprotein and a member of the immunoglobulin superfamily which exists in both a membrane-spanning and a soluble form. Homotypic interactions of EMMPRIN underlie its multiple roles in normal development and pathological situations such as viral infections, Alzheimer's disease and cancer. This study employed a recombinant soluble, fully glycosylated EMMPRIN domain (rhsEMN) as a tool to characterize the structural basis of EMMPRIN-EMMPRIN receptor (EMNR) contacts and their functional effects on MCF-7 breast carcinoma cells. rhsEMN did not form dimers in solution but bound to surface EMMPRIN (EMN) on MCF-7 cells with high affinity and was readily internalized. The interaction interface for the homotypic contact was localized to the N-terminal Ig domain. rhsEMN exerted a stimulatory effect on proliferation of MCF-7 cells whereas it reduced cell migration in a dose-dependent manner. These effects were accompanied by an upregulation of endogenous EMMPRIN as well as of matrix metalloproteinase-14 (MMP-14), a membrane-bound protease involved in the extracellular release of soluble EMMPRIN, indicating a regulatory feedback mechanism. The proliferation-promoting activity of rhsEMN was mimicked by a novel functional antibody directed to EMMPRIN, underscoring that crosslinking of cell surface EMMPRIN (EMNR) is crucial for eliciting intracellular signalling. Addressing malignancy-related signal transduction in HEK-293 cells, we could show that rhsEMN triggers the oncogenic Wnt pathway. © 2015 FEBS.

  20. Gender differences in associations between cancer-related problems and relationship dissolution among cancer survivors.

    Science.gov (United States)

    Stephens, Cristina; Westmaas, J Lee; Kim, Jihye; Cannady, Rachel; Stein, Kevin

    2016-10-01

    Research suggests that a cancer diagnosis predicts marital dissolution more strongly for women survivors than men, but there is a paucity of research on potential processes underlying this vulnerability. The present cross-sectional study examined whether specific cancer-related problems were associated with the odds of relationship breakup following diagnosis and whether these relationships differed between male and female cancer survivors. A national cross-sectional quality of life study assessed self-reported cancer-related problems and relationship change among survivors who were either 2, 6, or 10 years post-diagnosis (n = 6099). Bivariate analyses indicated that cancer-related problems (e.g., emotional distress) were greater for divorced/separated survivors compared to those with intact relationships and were greater for women versus men. Logistic regressions indicated that for both male and female survivors, lower income, younger age, and longer time since diagnosis were associated with greater odds of divorce or separation after diagnosis (ORs > 2.14, p emotional distress (OR = 1.14, p divorce or separation. For men only, fear of cancer recurrence was associated with greater odds of divorce or separation (OR = 1.32, p emotional or financial/employment problems attributed to the cancer diagnosis were associated with the likelihood of reporting relationship dissolution. Although directions of causality could not be ascertained, results suggest the possibility that helping male and female cancer survivors cope with specific cancer-related problems may benefit the quality and stability of their relationships with significant others following diagnosis.

  1. Health-related quality of life in early breast cancer

    DEFF Research Database (Denmark)

    Grønvold, Mogens

    2010-01-01

    The treatment of primary breast cancer usually consists of surgery often followed by adjuvant therapy (radiotherapy, chemotherapy, hormonal treatment, etc.) to reduce the risk of recurrence. The cancer diagnosis and the treatments may have significant impact on the patients' quality of life....... This thesis deals with scientific aspects and clinical results of a study aimed at assessing the impact of breast cancer (and its treatment) on the patients' quality of life. Studies such as this assessing the problems and symptoms experienced by the patients are often referred to as health-related quality...... study to be impaired in patients receiving chemotherapy. Similarly, current review articles on HRQL effects of adjuvant chemotherapy mention only relatively few of these topics. Concerning HRQL after the treatment period, our main finding was that many symptoms and problems had declined or disappeared...

  2. Supporting cancer patients and their relatives through storytelling

    DEFF Research Database (Denmark)

    la Cour, Karen; Ledderer, Loni; Hansen, Helle Ploug

    2016-01-01

    observations, informal conversations and follow-up interviews conducted one month after completing the intervention. Analysis was performed drawing on narrative theory combined with social practice theory. The results demonstrate that the use of storytelling and metaphors intertwined with other course...... activities, such as dancing and arts & crafts, provided the patients and their relatives with strategies to manage cancer-related concerns, which they were later able to apply in their everyday lives. The study results may be useful to other professionals in clinical practice for rehabilitation purposes......Previous research on psychosocial support for cancer-related concerns has primarily focused on either patients or their relatives, although limited research is available on how patients and their relatives can be supported together. The aim of this article is to explore the use of storytelling...

  3. Measurement of Glycosylated Alpha-Fetoprotein Improves Diagnostic Power over the Native Form in Hepatocellular Carcinoma

    Science.gov (United States)

    Jin, Jonghwa; Park, Jiyoung; Yu, Su Jong; Yoon, Jung-Hwan; Kim, Youngsoo

    2014-01-01

    Serum alpha-fetoprotein (AFP) has long been used as a diagnostic marker for hepatocellular carcinoma (HCC), albeit controversially. Although it remains widely used in clinics, the value of AFP in HCC diagnosis has recently been challenged due to its significant rates of false positive and false negative findings. To improve the efficacy of AFP as HCC diagnostic marker, we developed a method of measuring total and glycosylated AFP by multiple reaction monitoring (MRM)-MS. In this study, we verified the total amount of AFP (nonglycopeptide levels) and the degree of glycosylated AFP (deglycopeptide levels) in 60 normal (41 men and 19 women; mean age 53 years; range 32–74 years), 35 LC (23 men and 12 women; mean age 56 years; range 43–78 years; HBV-related), and 60 HCC subjects (42 men and 18 women; mean age 58 years; range 38–76 years; HBV-related; 30 stage I, 15 stage II, and 10 stage III). By MRM-MS analysis, the nonglycopeptide had 56.7% sensitivity, 68.3% specificity, and an AUC of 0.687 [cutoff value: ≥0.02 (light/heavy ratio)], comparing the normal and HCC group, whereas the deglycopeptide had 93.3% sensitivity, 68.3% specificity, and an AUC of 0.859 [cutoff value: ≥0.02 (light/heavy ratio)]. In comparing the stage I HCC subgroup with the LC group, the nonglycopeptide had a sensitivity of 66.7%, specificity of 80.0%, and an AUC of 0.712 [cutoff value: ≥0.02 (light/heavy ratio)], whereas the deglycopeptide had a sensitivity of 96.7%, specificity of 80.0%, and an AUC of 0.918 [cutoff value: ≥0.02 (light/heavy ratio)]. These data demonstrate that the discriminatory power of the deglycopeptide is greater than that of the nonglycopeptide. We conclude that deglycopeptide can distinguish cancer status between normal subjects and HCC patients better than nonglycopeptide. PMID:25310463

  4. Method Development in the Regioselective Glycosylation of Unprotected Carbohydrates

    DEFF Research Database (Denmark)

    Niedbal, Dominika Alina

    and the glycosylations were promoted by tetrabutylammonium bromide. The couplings were completely selective and gave rise to a number of 1,6-linked disaccharides with 1,2- cis-linked orientation. Project 2: Boron-mediated glycosylation of unprotected carbohydrates Boron-mediated regioselective Koenigs...

  5. N-linked glycosylation of the immunoglobulin variable region

    NARCIS (Netherlands)

    van de Bovenkamp, Fleur S.; Derksen, Ninotska I. L.; Ooijevaar-de Heer, Pleuni; van Schie, Karin A.; Kruithof, Simone; Berkowska, Magdalena A.; van der Schoot, C. Ellen; Ijspeert, Hanna; van der Burg, Mirjam; Gils, Ann; Hafkenscheid, Lise; Toes, René E. M.; Rombouts, Yoann; Plomp, Rosina; Wuhrer, Manfred; van Ham, S. Marieke; Vidarsson, Gestur; Rispens, Theo

    2018-01-01

    N-glycosylation sites are introduced at positions in which glycans can affect antigen binding as a result of a specific clustering of progenitor glycosylation sites in the germline sequences of variable domain genes. By analyzing multiple human monoclonal and polyclonal (auto)antibody responses, we

  6. Trans-species Engineering of Glycosylated Therapeutic Proteins

    DEFF Research Database (Denmark)

    Yang, Zhang

    eukaryotes and even prokaryotes. Insect and yeast cells produce O-glycosylation incompatible with use in humans, however recently the yeast Pichia was engineered to perform the first step of human-like O-glycosylation. This review provides an overview of past and current engineering efforts of N...

  7. Analysis and metabolic engineering of lipid-linked oligosaccharides in glycosylation-deficient CHO cells

    International Nuclear Information System (INIS)

    Jones, Meredith B.; Tomiya, Noboru; Betenbaugh, Michael J.; Krag, Sharon S.

    2010-01-01

    Glycosylation-deficient Chinese Hamster Ovary (CHO) cell lines can be used to expand our understanding of N-glycosylation pathways and to study Congenital Disorders of Glycosylation, diseases caused by defects in the synthesis of N-glycans. The mammalian N-glycosylation pathway involves the step-wise assembly of sugars onto a dolichol phosphate (P-Dol) carrier, forming a lipid-linked oligosaccharide (LLO), followed by the transfer of the completed oligosaccharide onto the protein of interest. In order to better understand how deficiencies in this pathway affect the availability of the completed LLO donor for use in N-glycosylation, we used a non-radioactive, HPLC-based assay to examine the intermediates in the LLO synthesis pathway for CHO-K1 cells and for three different glycosylation-deficient CHO cell lines. B4-2-1 cells, which have a mutation in the dolichol phosphate-mannose synthase (DPM2) gene, accumulated LLO with the structure Man 5 GlcNAc 2 -P-P-Dol, while MI8-5 cells, which lack glucosyltransferase I (ALG6) activity, accumulated Man 9 GlcNAc 2 -P-P-Dol. CHO-K1 and MI5-4 cells both produced primarily the complete LLO, Glc 3 Man 9 GlcNAc 2 -P-P-Dol, though the relative quantity was lower in MI5-4. MI5-4 cells have reduced hexokinase activity which could affect the availability of many of the substrates required for LLO synthesis and, consequently, impair production of the final LLO donor. Increasing hexokinase activity by overexpressing hexokinase II in MI5-4 caused a decrease in the relative quantities of the incomplete LLO intermediates from Man 5 GlcNAc 2 -PP-Dol through Glc 1 Man 9 GlcNAc 2 -PP-Dol, and an increase in the relative quantity of the final LLO donor, Glc 3 Man 9 GlcNAc 2 -P-P-Dol. This study suggests that metabolic engineering may be a useful strategy for improving LLO availability for use in N-glycosylation.

  8. Analysis and metabolic engineering of lipid-linked oligosaccharides in glycosylation-deficient CHO cells

    Energy Technology Data Exchange (ETDEWEB)

    Jones, Meredith B., E-mail: mbauman7@jhu.edu [Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Maryland Hall 221, Baltimore, MD 21218 (United States); Tomiya, Noboru, E-mail: ntomiya1@jhu.edu [Department of Biology, Johns Hopkins University, 3400 North Charles Street, Mudd Hall 104A, Baltimore, MD 21218 (United States); Betenbaugh, Michael J., E-mail: beten@jhu.edu [Department of Chemical and Biomolecular Engineering, Johns Hopkins University, 3400 North Charles Street, Maryland Hall 221, Baltimore, MD 21218 (United States); Krag, Sharon S., E-mail: skrag@jhsph.edu [Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205 (United States)

    2010-04-23

    Glycosylation-deficient Chinese Hamster Ovary (CHO) cell lines can be used to expand our understanding of N-glycosylation pathways and to study Congenital Disorders of Glycosylation, diseases caused by defects in the synthesis of N-glycans. The mammalian N-glycosylation pathway involves the step-wise assembly of sugars onto a dolichol phosphate (P-Dol) carrier, forming a lipid-linked oligosaccharide (LLO), followed by the transfer of the completed oligosaccharide onto the protein of interest. In order to better understand how deficiencies in this pathway affect the availability of the completed LLO donor for use in N-glycosylation, we used a non-radioactive, HPLC-based assay to examine the intermediates in the LLO synthesis pathway for CHO-K1 cells and for three different glycosylation-deficient CHO cell lines. B4-2-1 cells, which have a mutation in the dolichol phosphate-mannose synthase (DPM2) gene, accumulated LLO with the structure Man{sub 5}GlcNAc{sub 2}-P-P-Dol, while MI8-5 cells, which lack glucosyltransferase I (ALG6) activity, accumulated Man{sub 9}GlcNAc{sub 2}-P-P-Dol. CHO-K1 and MI5-4 cells both produced primarily the complete LLO, Glc{sub 3}Man{sub 9}GlcNAc{sub 2}-P-P-Dol, though the relative quantity was lower in MI5-4. MI5-4 cells have reduced hexokinase activity which could affect the availability of many of the substrates required for LLO synthesis and, consequently, impair production of the final LLO donor. Increasing hexokinase activity by overexpressing hexokinase II in MI5-4 caused a decrease in the relative quantities of the incomplete LLO intermediates from Man{sub 5}GlcNAc{sub 2}-PP-Dol through Glc{sub 1}Man{sub 9}GlcNAc{sub 2}-PP-Dol, and an increase in the relative quantity of the final LLO donor, Glc{sub 3}Man{sub 9}GlcNAc{sub 2}-P-P-Dol. This study suggests that metabolic engineering may be a useful strategy for improving LLO availability for use in N-glycosylation.

  9. Effect of aerobic exercise on cancer-related fatigue

    Directory of Open Access Journals (Sweden)

    Jaivika Govindbhai Patel

    2017-01-01

    Full Text Available Background: Fatigue is the most common side effect of cancer treatment with chemotherapy and/or radiation therapy, selected biologic response modifiers. The main purpose of this study is to evaluate the effects of aerobic exercise on cancer-related fatigue in patients of the solid tumor after chemotherapy and radiotherapy. Methods: After screening for cancer-related fatigue, 34 patients fulfilled the inclusive criteria and were assigned into two groups (n = 17 recruited in the intervention group and n = 17 in control group. The intervention group received aerobic exercise program which included treadmill walking with low to moderate intensity (50%–70% of maximum heart rate, for 20–40 min/day for 5 days/week. Control group were taught stretching exercises of hamstrings, gastrocnemius, and soleus (to be done at home and were encouraged to remain active. Outcome measures such as brief fatigue inventory (BFI, 6-min walk test, and functional assessment of cancer therapy-general (FACT-G were taken at baseline and after 6-weeks. Results: The data were analyzed using the Wilcoxon matched-pairs signed rank test for within group and Mann–Whitney U-test for between group comparisons. The results of this study showed that there was a significant reduction in cancer-related fatigue BFI score (P < 0.0001,, also there was significant improvement in the physical performance as in 6-min walk distance (P < 0.0001 and quality of life, FACT-G score (P = 0.0001. Conclusion: Aerobic exercise for 6 weeks has beneficial effects on cancer-related fatigue in patients with solid tumor after chemotherapy and/or radiotherapy.

  10. Trans-species Engineering of Glycosylated Therapeutic Proteins

    DEFF Research Database (Denmark)

    Yang, Zhang

    important to address. Whenever glycosylation has been found to be an important PTM for function or bioactivity, human therapeutics have generally been produced in mammalian Chinese hamster ovary (CHO) cell line. Oglycosylation is one of the most complex regulated PTMs of proteins but also one of the least...... understood. Currently, mammalian cells are required for human O-glycosylation. Increasing efforts have been devoted to engineering non-mammalian cells for production of recombinant proteins with “human-like” glycosylation. Substantial success has been achieved with designed N-glycosylation in both lower......Recombinant expression of therapeutic proteins is one of the major tasks in modern biomedicine. One of the most important factors with respect to therapeutic use in human is posttranslational modifications (PTMs) of the recombinant proteins, of which protein glycosylation is by far the most...

  11. Nutritional Therapies in Congenital Disorders of Glycosylation (CDG

    Directory of Open Access Journals (Sweden)

    Peter Witters

    2017-11-01

    Full Text Available Congenital disorders of glycosylation (CDG are a group of more than 130 inborn errors of metabolism affecting N-linked, O-linked protein and lipid-linked glycosylation. The phenotype in CDG patients includes frequent liver involvement, especially the disorders belonging to the N-linked protein glycosylation group. There are only a few treatable CDG. Mannose-Phosphate Isomerase (MPI-CDG was the first treatable CDG by high dose mannose supplements. Recently, with the successful use of d-galactose in Phosphoglucomutase 1 (PGM1-CDG, other CDG types have been trialed on galactose and with an increasing number of potential nutritional therapies. Current mini review focuses on therapies in glycosylation disorders affecting liver function and dietary intervention in general in N-linked glycosylation disorders. We also emphasize now the importance of early screening for CDG in patients with mild hepatopathy but also in cholestasis.

  12. a survey on drug related problems in cervical cancer patients

    African Journals Online (AJOL)

    userpc

    Cisplatin/5FU/paclitaxel. 6. 9.23. 6. Seizure. Cisplatin. 2. 3.08. 7. Loss of hair. Cisplatin/5FU/Paclitaxel. 3. 4.62. 8. Nephrotoxicity. Cisplatin. 3. 4.62. 9. Hypotension. Paclitaxel. 3. 4.62. TOTAL. 65. 100. Table 3: Relationship between cervical cancer patients' factors and DRPs. Patients Factor. Drug Related Problems (DRPs).

  13. Differential dependence on N-glycosylation of anthrax toxin receptors CMG2 and TEM8.

    Directory of Open Access Journals (Sweden)

    Sarah Friebe

    Full Text Available ANTXR 1 and 2, also known as TEM8 and CMG2, are two type I membrane proteins, which have been extensively studied for their role as anthrax toxin receptors, but with a still elusive physiological function. Here we have analyzed the importance of N-glycosylation on folding, trafficking and ligand binding of these closely related proteins. We find that TEM8 has a stringent dependence on N-glycosylation. The presence of at least one glycan on each of its two extracellular domains, the vWA and Ig-like domains, is indeed necessary for efficient trafficking to the cell surface. In the absence of any N-linked glycans, TEM8 fails to fold correctly and is recognized by the ER quality control machinery. Expression of N-glycosylation mutants reveals that CMG2 is less vulnerable to sugar loss. The absence of N-linked glycans in one of the extracellular domains indeed has little impact on folding, trafficking or receptor function of the wild type protein expressed in tissue culture cells. N-glycans do, however, seem required in primary fibroblasts from human patients. Here, the presence of N-linked sugars increases the tolerance to mutations in cmg2 causing the rare genetic disease Hyaline Fibromatosis Syndrome. It thus appears that CMG2 glycosylation provides a buffer towards genetic variation by promoting folding of the protein in the ER lumen.

  14. Altered protein glycosylation predicts Alzheimer's disease and modulates its pathology in disease model Drosophila.

    Science.gov (United States)

    Frenkel-Pinter, Moran; Stempler, Shiri; Tal-Mazaki, Sharon; Losev, Yelena; Singh-Anand, Avnika; Escobar-Álvarez, Daniela; Lezmy, Jonathan; Gazit, Ehud; Ruppin, Eytan; Segal, Daniel

    2017-08-01

    The pathological hallmarks of Alzheimer's disease (AD) are pathogenic oligomers and fibrils of misfolded amyloidogenic proteins (e.g., β-amyloid and hyper-phosphorylated tau in AD), which cause progressive loss of neurons in the brain and nervous system. Although deviations from normal protein glycosylation have been documented in AD, their role in disease pathology has been barely explored. Here our analysis of available expression data sets indicates that many glycosylation-related genes are differentially expressed in brains of AD patients compared with healthy controls. The robust differences found enabled us to predict the occurrence of AD with remarkable accuracy in a test cohort and identify a set of key genes whose expression determines this classification. We then studied in vivo the effect of reducing expression of homologs of 6 of these genes in transgenic Drosophila overexpressing human tau, a well-established invertebrate AD model. These experiments have led to the identification of glycosylation genes that may augment or ameliorate tauopathy phenotypes. Our results indicate that OstDelta, l(2)not and beta4GalT7 are tauopathy suppressors, whereas pgnat5 and CG33303 are enhancers, of tauopathy. These results suggest that specific alterations in protein glycosylation may play a causal role in AD etiology. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylated variants of a single polypeptide chain.

    Science.gov (United States)

    Murphy, P A; Cebula, T A; Windle, B E

    1981-10-01

    Rabbit endogenous pyrogens were of about the same molecular size, but showed considerable heterogeneity of their isoelectric points. We attempted to show that this heterogeneity was attributable to variable glycosylation of a single polypeptide chain. When peritoneal exudate cells were stimulated to make pyrogens in the presence of 2-deoxy-D-glucose, there was a relatively trivial suppression of pyrogen release, and analysis by isoelectric focusing showed parallel inhibition of secretion of all the forms of endogenous pyrogen. When cells were stimulated in the presence of 3H-labeled amino acids and 14C-labeled glucosamine or glucose, the purified pyrogens were labeled with 3H but not with 14C. Macrophage membrane preparations were made which contained glycosyl transferases and could transfer sugar residues from sugar nucleotides to deglycosylated fetuin. These macrophage membrane preparations did not transfer sugars to the pI 7.3 endogenous pyrogen. Treatment of endogenous pyrogens with neuraminidase or with periodate produced no evidence suggesting that the pyrogens were glycosylated. Last, endogenous pyrogens did not bind to any of four lectins with different carbohydrate specificities. This evidence suggests that the heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylation and must have some other cause.

  16. Effects of scheduled exercise on cancer-related fatigue in women with early breast cancer

    OpenAIRE

    Husebø, Anne Marie Lunde; Dyrstad, Sindre Mikal; Mjaaland, Ingvil; Søreide, Jon Arne; Bru, Lars Edvin

    2014-01-01

    The article was originally published in The Scientific World Journal; by Hindawi Publishing Corporation under the Creative Commons Attribution License; see http://dx.doi.org/10.1155/2014/27182. While physical activity during cancer treatment is found beneficial for breast cancer patients, evidence indicates ambiguous findings concerning effects of scheduled exercise programs on treatment-related symptoms. This study investigated effects of a scheduled home-based exercise intervention i...

  17. Supervised exercise reduces cancer-related fatigue: a systematic review

    Directory of Open Access Journals (Sweden)

    José F Meneses-Echávez

    2015-01-01

    Full Text Available Question: Does supervised physical activity reduce cancer-related fatigue? Design: Systematic review with meta-analysis of randomised trials. Participants: People diagnosed with any type of cancer, without restriction to a particular stage of diagnosis or treatment. Intervention: Supervised physical activity interventions (eg, aerobic, resistance and stretching exercise, defined as any planned or structured body movement causing an increase in energy expenditure, designed to maintain or enhance health-related outcomes, and performed with systematic frequency, intensity and duration. Outcome measures: The primary outcome measure was fatigue. Secondary outcomes were physical and functional wellbeing assessed using the Functional Assessment of Cancer Therapy Fatigue Scale, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Piper Fatigue Scale, Schwartz Cancer Fatigue Scale and the Multidimensional Fatigue Inventory. Methodological quality, including risk of bias of the studies, was evaluated using the PEDro Scale. Results: Eleven studies involving 1530 participants were included in the review. The assessment of quality showed a mean score of 6.5 (SD 1.1, indicating a low overall risk of bias. The pooled effect on fatigue, calculated as a standardised mean difference (SMD using a random-effects model, was –1.69 (95% CI –2.99 to –0.39. Beneficial reductions in fatigue were also found with combined aerobic and resistance training with supervision (SMD = –0.41, 95% CI –0.70 to –0.13 and with combined aerobic, resistance and stretching training with supervision (SMD = –0.67, 95% CI –1.17 to –0.17. Conclusion: Supervised physical activity interventions reduce cancer-related fatigue. These findings suggest that combined aerobic and resistance exercise regimens with or without stretching should be included as part of rehabilitation programs for people who have been diagnosed with cancer

  18. Ozone depletion, related UVB changes and increased skin cancer incidence

    Science.gov (United States)

    Kane, R. P.

    1998-03-01

    Stratospheric ozone at middle latitudes shows a seasonal variation of about +/-20%, a quasi-biennial oscillation of 1-10% range and a long-term variation in which the level was almost steady up to about 1979 and declined thereafter to the present day by about 10%. These variations are expected to be reflected in solar UVB observed at the ground, but in an opposite direction. Thus UVB should have had a long-term increase of about 10-20%, which should cause an increase in skin cancer incidence of about 20-40%. Skin cancer incidence has increased all over the world, e.g. about 90% in USA during 1974-1990. It is popularly believed that this increase in skin cancer incidence is related to the recent ozone depletion. This seems to be incorrect, for two reasons. Firstly, the observed skin cancer increase is too large (90%) compared with the expected value (40%) from ozone depletion. Secondly, cancer does not develop immediately after exposure to solar UVB. The sunburns may occur within hours; but cancer development and detection may take years, even decades. Hence the observed skin cancer increase since 1974 (no data available for earlier periods) must have occurred due to exposure to solar UVB in the 1950s and 1960s, when there was no ozone depletion. Thus, the skin cancer increase must be attributed to harmful solar UVB levels existing even in the 1960s, accentuated later not by ozone depletion (which started only much later, by 1979) but by other causes, such as a longer human life span, better screening, increasing tendencies of sunbathing at beaches, etc., in affluent societies. On the other hand, the recent ozone depletion and the associated UVB increases will certainly take their toll; only that the effects will not be noticed now but years or decades from now. The concern for the future expressed in the Montreal Protocol for reducing ozone depletion by controlling CFC production is certainly justified, especially because increased UVB is harmful to animal and

  19. Classification of Cancer-related Death Certificates using Machine Learning

    Directory of Open Access Journals (Sweden)

    Luke Butt

    2013-05-01

    Full Text Available BackgroundCancer monitoring and prevention relies on the critical aspect of timely notification of cancer cases. However, the abstraction and classification of cancer from the free-text of pathology reports and other relevant documents, such as death certificates, exist as complex and time-consuming activities.AimsIn this paper, approaches for the automatic detection of notifiable cancer cases as the cause of death from free-text death certificates supplied to Cancer Registries are investigated.Method A number of machine learning classifiers were studied. Features were extracted using natural language techniques and the Medtex toolkit. The numerous features encompassed stemmed words, bi-grams, and concepts from the SNOMED CT medical terminology. The baseline consisted of a keyword spotter using keywords extracted from the long description of ICD-10 cancer related codes.ResultsDeath certificates with notifiable cancer listed as the cause of death can be effectively identified with the methods studied in this paper. A Support Vector Machine (SVM classifier achieved best performance with an overall F-measure of 0.9866 when evaluated on a set of 5,000 free-text death certificates using the token stem feature set. The SNOMED CT concept plus token stem feature set reached the lowest variance (0.0032 and false negative rate (0.0297 while achieving an F-measure of 0.9864. The SVM classifier accounts for the first 18 of the top 40 evaluated runs, and entails the most robust classifier with a variance of 0.001141, half the variance of the other classifiers.ConclusionThe selection of features significantly produced the most influences on the performance of the classifiers, although the type of classifier employed also affects performance. In contrast, the feature weighting schema created a negligible effect on performance. Specifically, it is found that stemmed tokens with or without SNOMED CT concepts create the most effective feature when combined with

  20. MicroRNA Related Polymorphisms and Breast Cancer Risk

    Science.gov (United States)

    Khan, Sofia; Greco, Dario; Michailidou, Kyriaki; Milne, Roger L.; Muranen, Taru A.; Heikkinen, Tuomas; Aaltonen, Kirsimari; Dennis, Joe; Bolla, Manjeet K.; Liu, Jianjun; Hall, Per; Irwanto, Astrid; Humphreys, Keith; Li, Jingmei; Czene, Kamila; Chang-Claude, Jenny; Hein, Rebecca; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fletcher, Olivia; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Gibson, Lorna; Aitken, Zoe; Hopper, John L.; Tsimiklis, Helen; Bui, Minh; Makalic, Enes; Schmidt, Daniel F.; Southey, Melissa C.; Apicella, Carmel; Stone, Jennifer; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A.; van der Luijt, Rob B.; Meindl, Alfons; Schmutzler, Rita K.; Müller-Myhsok, Bertram; Lichtner, Peter; Turnbull, Clare; Rahman, Nazneen; Chanock, Stephen J.; Hunter, David J.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Schmidt, Marjanka K.; Broeks, Annegien; Veer, Laura J. V. a. n't.; Hogervorst, Frans B.; Fasching, Peter A.; Schrauder, Michael G.; Ekici, Arif B.; Beckmann, Matthias W.; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Benitez, Javier; Zamora, Pilar M.; Perez, Jose I. A.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Pharoah, Paul D. P.; Dunning, Alison M.; Shah, Mitul; Luben, Robert; Brown, Judith; Couch, Fergus J.; Wang, Xianshu; Vachon, Celine; Olson, Janet E.; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Mulot, Claire; Marme, Frederick; Burwinkel, Barbara; Schneeweiss, Andreas; Sohn, Christof; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Andrulis, Irene L.; Knight, Julia A.; Tchatchou, Sandrine; Mulligan, Anna Marie; Dörk, Thilo; Bogdanova, Natalia V.; Antonenkova, Natalia N.; Anton-Culver, Hoda; Darabi, Hatef; Eriksson, Mikael; Garcia-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; van Asperen, Christi J.; Kristensen, Vessela N.; Slager, Susan; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Lindblom, Annika; Margolin, Sara; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Mariani, Paolo; Hooning, Maartje J.; Martens, John W. M.; Collée, J. Margriet; Jager, Agnes; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Giles, Graham G.; McLean, Catriona; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Mannermaa, Arto; Hamann, Ute; Chenevix-Trench, Georgia; Blomqvist, Carl; Aittomäki, Kristiina; Easton, Douglas F.; Nevanlinna, Heli

    2014-01-01

    Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88–0.96), rs1052532 (OR 0.97; 95% CI: 0.95–0.99), rs10719 (OR 0.97; 95% CI: 0.94–0.99), rs4687554 (OR 0.97; 95% CI: 0.95–0.99, and rs3134615 (OR 1.03; 95% CI: 1.01–1.05) located in the 3′ UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects. PMID:25390939

  1. MicroRNA related polymorphisms and breast cancer risk.

    Science.gov (United States)

    Khan, Sofia; Greco, Dario; Michailidou, Kyriaki; Milne, Roger L; Muranen, Taru A; Heikkinen, Tuomas; Aaltonen, Kirsimari; Dennis, Joe; Bolla, Manjeet K; Liu, Jianjun; Hall, Per; Irwanto, Astrid; Humphreys, Keith; Li, Jingmei; Czene, Kamila; Chang-Claude, Jenny; Hein, Rebecca; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Fletcher, Olivia; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Gibson, Lorna; Aitken, Zoe; Hopper, John L; Tsimiklis, Helen; Bui, Minh; Makalic, Enes; Schmidt, Daniel F; Southey, Melissa C; Apicella, Carmel; Stone, Jennifer; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A; van der Luijt, Rob B; Meindl, Alfons; Schmutzler, Rita K; Müller-Myhsok, Bertram; Lichtner, Peter; Turnbull, Clare; Rahman, Nazneen; Chanock, Stephen J; Hunter, David J; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Schmidt, Marjanka K; Broeks, Annegien; Van't Veer, Laura J; Hogervorst, Frans B; Fasching, Peter A; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Benitez, Javier; Zamora, Pilar M; Perez, Jose I A; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Pharoah, Paul D P; Dunning, Alison M; Shah, Mitul; Luben, Robert; Brown, Judith; Couch, Fergus J; Wang, Xianshu; Vachon, Celine; Olson, Janet E; Lambrechts, Diether; Moisse, Matthieu; Paridaens, Robert; Christiaens, Marie-Rose; Guénel, Pascal; Truong, Thérèse; Laurent-Puig, Pierre; Mulot, Claire; Marme, Frederick; Burwinkel, Barbara; Schneeweiss, Andreas; Sohn, Christof; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Andrulis, Irene L; Knight, Julia A; Tchatchou, Sandrine; Mulligan, Anna Marie; Dörk, Thilo; Bogdanova, Natalia V; Antonenkova, Natalia N; Anton-Culver, Hoda; Darabi, Hatef; Eriksson, Mikael; Garcia-Closas, Montserrat; Figueroa, Jonine; Lissowska, Jolanta; Brinton, Louise; Devilee, Peter; Tollenaar, Robert A E M; Seynaeve, Caroline; van Asperen, Christi J; Kristensen, Vessela N; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Lindblom, Annika; Margolin, Sara; Radice, Paolo; Peterlongo, Paolo; Barile, Monica; Mariani, Paolo; Hooning, Maartje J; Martens, John W M; Collée, J Margriet; Jager, Agnes; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Giles, Graham G; McLean, Catriona; Brauch, Hiltrud; Brüning, Thomas; Ko, Yon-Dschun; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Swerdlow, Anthony; Ashworth, Alan; Orr, Nick; Jones, Michael; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Mannermaa, Arto; Hamann, Ute; Chenevix-Trench, Georgia; Blomqvist, Carl; Aittomäki, Kristiina; Easton, Douglas F; Nevanlinna, Heli

    2014-01-01

    Genetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS). Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC). Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER) and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR) 0.92; 95% confidence interval (CI): 0.88-0.96), rs1052532 (OR 0.97; 95% CI: 0.95-0.99), rs10719 (OR 0.97; 95% CI: 0.94-0.99), rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05) located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

  2. MicroRNA related polymorphisms and breast cancer risk.

    Directory of Open Access Journals (Sweden)

    Sofia Khan

    Full Text Available Genetic variations, such as single nucleotide polymorphisms (SNPs in microRNAs (miRNA or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility to cancer. We investigated associations between miRNA related SNPs and breast cancer risk. First we evaluated 2,196 SNPs in a case-control study combining nine genome wide association studies (GWAS. Second, we further investigated 42 SNPs with suggestive evidence for association using 41,785 cases and 41,880 controls from 41 studies included in the Breast Cancer Association Consortium (BCAC. Combining the GWAS and BCAC data within a meta-analysis, we estimated main effects on breast cancer risk as well as risks for estrogen receptor (ER and age defined subgroups. Five miRNA binding site SNPs associated significantly with breast cancer risk: rs1045494 (odds ratio (OR 0.92; 95% confidence interval (CI: 0.88-0.96, rs1052532 (OR 0.97; 95% CI: 0.95-0.99, rs10719 (OR 0.97; 95% CI: 0.94-0.99, rs4687554 (OR 0.97; 95% CI: 0.95-0.99, and rs3134615 (OR 1.03; 95% CI: 1.01-1.05 located in the 3' UTR of CASP8, HDDC3, DROSHA, MUSTN1, and MYCL1, respectively. DROSHA belongs to miRNA machinery genes and has a central role in initial miRNA processing. The remaining genes are involved in different molecular functions, including apoptosis and gene expression regulation. Further studies are warranted to elucidate whether the miRNA binding site SNPs are the causative variants for the observed risk effects.

  3. Treatment-related neuroendocrine prostate cancer resulting in Cushing's syndrome.

    Science.gov (United States)

    Ramalingam, Sundhar; Eisenberg, Adva; Foo, Wen Chi; Freedman, Jennifer; Armstrong, Andrew J; Moss, Larry G; Harrison, Michael R

    2016-12-01

    Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome. Molecular analysis of the patient's tumor through RNA sequencing showed high expression of several genes including CHGA, ASCL1, CALCA, HES6, PCSK1, CALCB and INSM1 confirming his neuroendocrine phenotype; elevated POMC expression was found, supporting the diagnosis of ectopic Cushing's syndrome. © 2016 The Japanese Urological Association.

  4. Lymphoedema management in breast cancer-related lymphoedema.

    Science.gov (United States)

    Jones, Joanne

    2013-04-01

    Due to developments in diagnosis and treatment of breast cancer, survival rates are rising. This leads to a population of mainly women, who also experience breast cancer-related lymphoedema (BCRL). Long after the cancer has been treated, lymphoedema persists at a time when individuals have returned to work. Large limb volumes can present a problem to these individuals and innovative treatments are needed, in order to retain as much normality as possible and reduce excessive limb volumes that patients can experience with lymphoedema long after treatment. It is also important that these treatments do not disrupt daily living and, for some, work-life balance. With the introduction of wrap around compression systems and collaborative working with the patient, it is possible to achieve an acceptable outcome to those patients with these issues. This approach leads to patient satisfaction and stabilisation of limb volume to within acceptable limits for these patients, in conjunction with the therapist.

  5. Robotic Radiosurgery. Treating prostata cancer and related genitourinary applications

    International Nuclear Information System (INIS)

    Ponsky, Lee E.

    2012-01-01

    Prostate cancer is the most common cancer among North American and European men, but its treatment continues to be problematic owing to serious side-effects, including erectile dysfunction, urinary incontinence, and potential lower GI complications. Robotic radiosurgery offers a novel, rapid, non-invasive outpatient treatment option for prostate cancer that combines robotics, advanced image-guided motion detection, and automated real-time corrective spatial positioning with submillimeter precision. This book examines all aspects of the treatment of prostate cancer with robotic radiosurgery. After introductory sections on radiosurgery as a multidisciplinary practice and specific issues relating to prostate cancer, the important challenge posed by prostate motion when administering radiation therapy is examined in depth, with detailed discussion as to how image-guided robotic radiosurgery overcomes this problem by continously identifying the precise location of the prostate throughout the course of treatment. A further major section is devoted to a discussion of techniques and potential radiobiological and clinical advantages of hypofractionated radiation delivery by means of robotic radiosurgery systems. The book closes by discussing other emerging genitourinary applications of robotic radiosurgery. All of the authors are experts in their field who present a persuasive case for this fascinating technique. (orig.)

  6. Robotic Radiosurgery. Treating prostata cancer and related genitourinary applications

    Energy Technology Data Exchange (ETDEWEB)

    Ponsky, Lee E. (ed.) [Case Western Reserve University School of Medicine, Cleveland, OH (United States). University Hospitals Case Medical Center

    2012-07-01

    Prostate cancer is the most common cancer among North American and European men, but its treatment continues to be problematic owing to serious side-effects, including erectile dysfunction, urinary incontinence, and potential lower GI complications. Robotic radiosurgery offers a novel, rapid, non-invasive outpatient treatment option for prostate cancer that combines robotics, advanced image-guided motion detection, and automated real-time corrective spatial positioning with submillimeter precision. This book examines all aspects of the treatment of prostate cancer with robotic radiosurgery. After introductory sections on radiosurgery as a multidisciplinary practice and specific issues relating to prostate cancer, the important challenge posed by prostate motion when administering radiation therapy is examined in depth, with detailed discussion as to how image-guided robotic radiosurgery overcomes this problem by continously identifying the precise location of the prostate throughout the course of treatment. A further major section is devoted to a discussion of techniques and potential radiobiological and clinical advantages of hypofractionated radiation delivery by means of robotic radiosurgery systems. The book closes by discussing other emerging genitourinary applications of robotic radiosurgery. All of the authors are experts in their field who present a persuasive case for this fascinating technique. (orig.)

  7. Financial Impact of Colorectal Cancer and Its Consequences: Associations Between Cancer-Related Financial Stress and Strain and Health-Related Quality of Life.

    Science.gov (United States)

    Sharp, Linda; O'Leary, Eamonn; O'Ceilleachair, Alan; Skally, Mairead; Hanly, Paul

    2018-01-01

    The financial impact and consequences of cancer on the lives of survivors remain poorly understood. This is especially true for colorectal cancer. We investigated objective cancer-related financial stress, subjective cancer-related financial strain, and their association with health-related quality of life in colorectal cancer survivors. This was a cross-sectional postal survey. The study was conducted in Ireland, which has a mixed public-private healthcare system. Colorectal cancer survivors, diagnosed 6 to 37 months prior, were identified from the population-based National Cancer Registry. Cancer-related financial stress was assessed as impact of cancer on household ability to make ends meet and cancer-related financial strain by feelings about household financial situation since cancer diagnosis. Health-related quality of life was based on European Organisation for Research and Treatment of Cancer QLQ-C30 global health status. Logistic regression was used to identify associations between financial stress and strain and low health-related quality of life (lowest quartile, score ≤50). A total of 493 survivors participated. Overall, 41% reported cancer-related financial stress and 39% cancer-related financial strain; 32% reported both financial stress and financial strain. After adjustment for sociodemographic and clinical variables, the odds of low health-related quality of life were significantly higher in those who reported cancer-related financial stress postdiagnosis compared with those who reported no change in financial stress postcancer (OR = 2.54 (95% CI, 1.62-3.99)). The odds of low health-related quality of life were also significantly higher in those with worse financial strain postdiagnosis (OR =1.73 (95% CI, 1.09-2.72)). The OR for those with both cancer-related financial stress and financial strain was 2.59 (95% CI, 1.59-4.22). Survey responders were younger, on average, than nonresponders. Responders and nonresponders may have differed in cancer-related

  8. A Knowledge-Based System for Display and Prediction of O-Glycosylation Network Behaviour in Response to Enzyme Knockouts.

    Directory of Open Access Journals (Sweden)

    Andrew G McDonald

    2016-04-01

    Full Text Available O-linked glycosylation is an important post-translational modification of mucin-type protein, changes to which are important biomarkers of cancer. For this study of the enzymes of O-glycosylation, we developed a shorthand notation for representing GalNAc-linked oligosaccharides, a method for their graphical interpretation, and a pattern-matching algorithm that generates networks of enzyme-catalysed reactions. Software for generating glycans from the enzyme activities is presented, and is also available online. The degree distributions of the resulting enzyme-reaction networks were found to be Poisson in nature. Simple graph-theoretic measures were used to characterise the resulting reaction networks. From a study of in-silico single-enzyme knockouts of each of 25 enzymes known to be involved in mucin O-glycan biosynthesis, six of them, β-1,4-galactosyltransferase (β4Gal-T4, four glycosyltransferases and one sulfotransferase, play the dominant role in determining O-glycan heterogeneity. In the absence of β4Gal-T4, all Lewis X, sialyl-Lewis X, Lewis Y and Sda/Cad glycoforms were eliminated, in contrast to knockouts of the N-acetylglucosaminyltransferases, which did not affect the relative abundances of O-glycans expressing these epitopes. A set of 244 experimentally determined mucin-type O-glycans obtained from the literature was used to validate the method, which was able to predict up to 98% of the most common structures obtained from human and engineered CHO cell glycoforms.

  9. Secondary and multiple primary cancers relating radiation therapy for cancer of the oral region

    International Nuclear Information System (INIS)

    Horiuchi, Junichi; Shibuya, Hitoshi; Takeda, Masamune; Takagi, Minoru.

    1985-01-01

    Secondary and multiple primary cancers relating radiation therapy for squamous cell carcinoma (s.c.c.) of the oral region including lip, oral cavity and oropharynx were analyzed. Out of 1,197 patients with s.c.c. treated with radiation during about 30 years from 1955 to 1983 June, 56 patients (4.7 %) were regarded as double or multiple cancer. The multiple cancer (s.c.c.) was observed frequently in the multicentric zone such as hypopharynx, esophagus and bronchus as well as in other sites of the oral cavity; 67.7 % (42 out of 62 sites). Frequency of synchronous double cancers was increased in recent ten years; 47.1 % (16/34). Careful examination to the above mentioned multicentric zone leads to early detection of secondary cancer and could be expected cure of the disease. Although possibility of radiation-induced cancer could not be ruled out as for 17 patients with late recurrence (more than 8 years), different histologic diagnosis from s.c.c. was obtained in only one (malignant fibrous histiocytoma). Therefore, it was difficult to discriminate radiation-induced cancer from late recurrence in the present study. (author)

  10. Role of structure and glycosylation of adsorbed protein films in biolubrication.

    Directory of Open Access Journals (Sweden)

    Deepak H Veeregowda

    Full Text Available Water forms the basis of lubrication in the human body, but is unable to provide sufficient lubrication without additives. The importance of biolubrication becomes evident upon aging and disease, particularly under conditions that affect secretion or composition of body fluids. Insufficient biolubrication, may impede proper speech, mastication and swallowing, underlie excessive friction and wear of articulating cartilage surfaces in hips and knees, cause vaginal dryness, and result in dry, irritated eyes. Currently, our understanding of biolubrication is insufficient to design effective therapeutics to restore biolubrication. Aim of this study was to establish the role of structure and glycosylation of adsorbed protein films in biolubrication, taking the oral cavity as a model and making use of its dynamics with daily perturbations due to different glandular secretions, speech, drinking and eating, and tooth brushing. Using different surface analytical techniques (a quartz crystal microbalance with dissipation monitoring, colloidal probe atomic force microscopy, contact angle measurements and X-ray photo-electron spectroscopy, we demonstrated that adsorbed salivary conditioning films in vitro are more lubricious when their hydrophilicity and degree of glycosylation increase, meanwhile decreasing their structural softness. High-molecular-weight, glycosylated proteins adsorbing in loops and trains, are described as necessary scaffolds impeding removal of water during loading of articulating surfaces. Comparing in vitro and in vivo water contact angles measured intra-orally, these findings were extrapolated to the in vivo situation. Accordingly, lubricating properties of teeth, as perceived in 20 volunteers comprising of equal numbers of male and female subjects, could be related with structural softness and glycosylation of adsorbed protein films on tooth surfaces. Summarizing, biolubrication is due to a combination of structure and glycosylation

  11. Mapping Sites of O-Glycosylation and Fringe Elongation on Drosophila Notch*

    Science.gov (United States)

    Harvey, Beth M.; Rana, Nadia A.; Moss, Hillary; Leonardi, Jessica; Jafar-Nejad, Hamed; Haltiwanger, Robert S.

    2016-01-01

    Glycosylation of the Notch receptor is essential for its activity and serves as an important modulator of signaling. Three major forms of O-glycosylation are predicted to occur at consensus sites within the epidermal growth factor-like repeats in the extracellular domain of the receptor: O-fucosylation, O-glucosylation, and O-GlcNAcylation. We have performed comprehensive mass spectral analyses of these three types of O-glycosylation on Drosophila Notch produced in S2 cells and identified peptides containing all 22 predicted O-fucose sites, all 18 predicted O-glucose sites, and all 18 putative O-GlcNAc sites. Using semiquantitative mass spectral methods, we have evaluated the occupancy and relative amounts of glycans at each site. The majority of the O-fucose sites were modified to high stoichiometries. Upon expression of the β3-N-acetylglucosaminyltransferase Fringe with Notch, we observed varying degrees of elongation beyond O-fucose monosaccharide, indicating that Fringe preferentially modifies certain sites more than others. Rumi modified O-glucose sites to high stoichiometries, although elongation of the O-glucose was site-specific. Although the current putative consensus sequence for O-GlcNAcylation predicts 18 O-GlcNAc sites on Notch, we only observed apparent O-GlcNAc modification at five sites. In addition, we performed mass spectral analysis on endogenous Notch purified from Drosophila embryos and found that the glycosylation states were similar to those found on Notch from S2 cells. These data provide foundational information for future studies investigating the mechanisms of how O-glycosylation regulates Notch activity. PMID:27268051

  12. Storytelling as part of cancer rehabilitation to support cancer patients and their relatives.

    Science.gov (United States)

    la Cour, Karen; Ledderer, Loni; Hansen, Helle Ploug

    2016-01-01

    Previous research on psychosocial support for cancer-related concerns has primarily focused on either patients or their relatives, although limited research is available on how patients and their relatives can be supported together. The aim of this article is to explore the use of storytelling as a part of a residential cancer rehabilitation intervention for patients together with their relatives, with a specific focus on their management of cancer-related concerns. Ten pairs participated in the intervention and data were generated through ethnographic fieldwork, including participant observations, informal conversations and follow-up interviews conducted one month after completing the intervention. Analysis was performed drawing on narrative theory combined with social practice theory. The results demonstrate that the use of storytelling and metaphors intertwined with other course activities, such as dancing and arts & crafts, provided the patients and their relatives with strategies to manage cancer-related concerns, which they were later able to apply in their everyday lives. The study results may be useful to other professionals in clinical practice for rehabilitation purposes for addressing issues of fear and worry.

  13. Analysis of factors related to arm weakness in patients with breast cancer-related lymphedema.

    Science.gov (United States)

    Lee, Daegu; Hwang, Ji Hye; Chu, Inho; Chang, Hyun Ju; Shim, Young Hun; Kim, Jung Hyun

    2015-08-01

    The aim of this study was to evaluate the ratio of significant weakness in the affected arm of breast cancer-related lymphedema patients to their unaffected side. Another purpose was to identify factors related to arm weakness and physical function in patients with breast cancer-related lymphedema. Consecutive patients (n = 80) attended a single evaluation session following their outpatient lymphedema clinic visit. Possible independent factors (i.e., lymphedema, pain, psychological, educational, and behavioral) were evaluated. Handgrip strength was used to assess upper extremity muscle strength and the disabilities of arm, shoulder, and hand (DASH) questionnaire was used to assess upper extremity physical function. Multivariate logistic regression was performed using factors that had significant differences between the handgrip weakness and non-weakness groups. Out of the 80 patients with breast cancer-related lymphedema, 29 patients (36.3 %) had significant weakness in the affected arm. Weakness of the arm with lymphedema was not related to lymphedema itself, but was related to the fear of using the affected limb (odds ratio = 1.76, 95 % confidence interval = 1.30-2.37). Fears of using the affected limb and depression significantly contributed to the variance in DASH scores. Appropriate physical and psychological interventions, including providing accurate information and reassurance of physical activity safety, are necessary to prevent arm weakness and physical dysfunction in patients with breast cancer-related lymphedema.

  14. Colon cancer information as a source of exercise motivation for relatives of patients with colon cancer.

    Science.gov (United States)

    McGowan, Erin L; Prapavessis, Harry

    2010-12-01

    Using a Protection Motivation Theory (PMT) framework, this study examined whether factual colon cancer information is a meaningful source of exercise motivation for relatives of patients with colon cancer. One hundred sixty-six inactive relatives were randomly assigned to one of two treatment conditions: PMT group (intervention); and non-PMT group (attention control). At baseline (T1) participants completed demographic information, a questionnaire designed to assess their beliefs toward exercise and colon cancer as well as their exercise intentions. At T2 (one week following T1) participants watched one of two DVD videos that were created for the study. The intervention DVD contained exercise and colon cancer information that was yoked within the four major components of PMT: perceived vulnerability (PV); perceived severity (PS); response efficacy (RE); and self-efficacy (SE), while the attention control DVD contained general diet and cancer information. Immediately following watching the DVD, participants completed the same measures as in T1. Participants assigned to the PMT intervention group showed significant improvement in PV, RE, SE and exercise intentions, whereas participants assigned to the attention control group showed significant improvement only in RE. RE, SE, and PS made significant and unique contributions to prediction of exercise intention. Overall, the results of the present study demonstrate that a single exposure media intervention grounded in a PMT framework can change individuals' exercise and colon cancer beliefs, as well as change their exercise intentions. Implications of these findings and direction for future research are discussed.

  15. Engineering Mammalian Mucin-type O-Glycosylation in Plants

    DEFF Research Database (Denmark)

    Yang, Zhang; Drew, Damian P; Jørgensen, Bodil

    2012-01-01

    -glycans are attached to proteins, and which structures are formed, difficult. Because plants are devoid of GalNAc-type O-glycosylation, we have assessed requirements for establishing human GalNAc O-glycosylation de novo in plants with the aim of developing cell systems with custom-designed O-glycosylation capacity...... was glycosylated with up to three and five GalNAc residues when co-expressed with GalNAc-T2 and a combination of GalNAc-T2 and GalNAc-T4, respectively, as determined by mass spectrometry. O-Glycosylation was furthermore demonstrated on a tandem repeat of MUC16 and interferon a2b. In plants, prolines in certain...... classes of proteins are hydroxylated and further substituted with plant-specific O-glycosylation; unsubstituted hydroxyprolines were identified in our MUC1 construct. In summary, this study demonstrates that mammalian type O-glycosylation can be established in plants and that plants may serve as a host...

  16. Functional Analysis of Glycosylation of Zika Virus Envelope Protein

    Directory of Open Access Journals (Sweden)

    Camila R. Fontes-Garfias

    2017-10-01

    Full Text Available Summary: Zika virus (ZIKV infection causes devastating congenital abnormities and Guillain-Barré syndrome. The ZIKV envelope (E protein is responsible for viral entry and represents a major determinant for viral pathogenesis. Like other flaviviruses, the ZIKV E protein is glycosylated at amino acid N154. To study the function of E glycosylation, we generated a recombinant N154Q ZIKV that lacks the E glycosylation and analyzed the mutant virus in mammalian and mosquito hosts. In mouse models, the mutant was attenuated, as evidenced by lower viremia, decreased weight loss, and no mortality; however, knockout of E glycosylation did not significantly affect neurovirulence. Mice immunized with the mutant virus developed a robust neutralizing antibody response and were completely protected from wild-type ZIKV challenge. In mosquitoes, the mutant virus exhibited diminished oral infectivity for the Aedes aegypti vector. Collectively, the results demonstrate that E glycosylation is critical for ZIKV infection of mammalian and mosquito hosts. : Zika virus (ZIKV causes devastating congenital abnormities and Guillain-Barré syndrome. Fontes-Garfias et al. showed that the glycosylation of ZIKV envelope protein plays an important role in infecting mosquito vectors and pathogenesis in mouse. Keywords: Zika virus, glycosylation, flavivirus entry, mosquito transmission, vaccine

  17. Quantifying risk of penile prosthesis infection with elevated glycosylated hemoglobin.

    Science.gov (United States)

    Wilson, S K; Carson, C C; Cleves, M A; Delk, J R

    1998-05-01

    Elevation of glycosylated hemoglobin above levels of 11.5 mg.% has been considered a contraindication to penile prosthesis implantation in diabetic patients. We determine the predictive value of glycosylated hemoglobin A1C in penile prosthesis infections in diabetic and nondiabetic patients to confirm or deny this prevalent opinion. We conducted a 2-year prospective study of 389 patients, including 114 diabetics, who underwent 3-piece penile prosthesis implantation. All patients had similar preoperative preparation without regard to diabetic status, control or glycosylated hemoglobin A1C level. Risk of infection was statistically analyzed for diabetics versus nondiabetics, glycosylated hemoglobin A1C values above and below 11.5 mg.%, insulin dependent versus oral medication diabetics, and fasting blood sugars above and below 180 mg.%. Prosthesis infections developed in 10 diabetics (8.7%) and 11 nondiabetics (4.0%). No increased infection rate was observed in diabetics with high fasting sugars or diabetics on insulin. There was no statistically significant increased infection risk with increased levels of glycosylated hemoglobin A1C among all patients or among only the diabetics. In fact, there was no meaningful difference in the median or mean level of glycosylated hemoglobin A1C in the infected and noninfected patients regardless of diabetes. Use of glycosylated hemoglobin A1C values to identify and exclude surgical candidates with increased risk of infections is not proved by this study. Elevation of fasting sugar or insulin dependence also does not increase risk of infection in diabetics undergoing prosthesis implantation.

  18. HPV epigenetic mechanisms related to Oropharyngeal and Cervix cancers.

    Science.gov (United States)

    Di Domenico, Marina; Giovane, Giancarlo; Kouidhi, Soumaya; Iorio, Rosamaria; Romano, Maurizio; De Francesco, Francesco; Feola, Antonia; Siciliano, Camilla; Califano, Luigi; Giordano, Antonio

    2017-03-31

    Human Papilloma Virus infection is very frequent in humans and is mainly transmitted sexually. The majority of infections are transient and asymptomatic, however, if the infection persists, it can occur with a variety of injuries to skin and mucous membranes, depending on the type of HPV involved. Some types of HPV are classified as high oncogenic risk as associated with the onset of cancer. The tumors most commonly associated with HPV are cervical and oropharyngeal cancer, epigenetic mechanisms related to HPV infection include methylation changes to host and viral DNA and chromatin modification in host species. This review is focused about epigenethic mechanism, such as MiRNAs expression, related to cervix and oral cancer. Specifically it discuss about molecular markers associated to a more aggressive phenotype. In this way we will analyze genes involved in meiotic sinaptonemal complex, transcriptional factors, of orthokeratins, sinaptogirin, they are all expressed in cancer in a way not more dependent on cell differentiation but HPV-dependent.

  19. Hydrophobic Man-1-P derivatives correct abnormal glycosylation in Type I congenital disorder of glycosylation fibroblasts.

    Science.gov (United States)

    Eklund, Erik A; Merbouh, Nabyl; Ichikawa, Mie; Nishikawa, Atsushi; Clima, Jessica M; Dorman, James A; Norberg, Thomas; Freeze, Hudson H

    2005-11-01

    Patients with Type I congenital disorders of glycosylation (CDG-I) make incomplete lipid-linked oligosaccharides (LLO). These glycans are poorly transferred to proteins resulting in unoccupied glycosylation sequons. Mutations in phosphomannomutase (PMM2) cause CDG-Ia by reducing the activity of PMM, which converts mannose (Man)-6-P to Man-1-P before formation of GDP-Man. These patients have reduced Man-1-P and GDP-Man. To replenish intracellular Man-1-P pools in CDG-Ia cells, we synthesized two hydrophobic, membrane permeable acylated versions of Man-1-P and determined their ability to normalize LLO size and N-glycosylation in CDG-Ia fibroblasts. Both compounds, compound I (diacetoxymethyl 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl phosphate) (C-I) and compound II (diacetoxymethyl 2,3,4,6-tetra-O-ethyloxycarbonyl-alpha-D-mannopyranosyl phosphate) (C-II), contain two acetoxymethyl (CH2OAc) groups O-linked to phosphorous. C-I contains acetyl esters and C-II contains ethylcarbonate (CO2Et) esters on the Man residue. Both C-I and C-II normalized truncated LLO, but C-II was about 2-fold more efficient than C-I. C-II replenished the GDP-Man pool in CDG-Ia cells and was more efficiently incorporated into glycoproteins than exogenous Man at low concentrations (25-75 mM). In a glycosylation assay of DNaseI in CDG-Ia cells, C-II restored glycosylation to control cell levels. C-II also corrected impaired LLO biosynthesis in cells from a Dolichol (Dol)-P-Man deficient patient (CDG-Ie) and partially corrected LLO in cells from an ALG12 mannosyltransferase-deficient patient (CDG-Ig), whereas cells from an ALG3-deficient patient (CDG-Id) and from an MPDU1-deficient patient (CDG-If) were not corrected. These results validate the general concept of using pro-Man-1-P substrates as potential therapeutics for CDG-I patients.

  20. Symptom report in detecting breast cancer-related lymphedema

    Directory of Open Access Journals (Sweden)

    Fu MR

    2015-10-01

    Full Text Available Mei R Fu,1 Deborah Axelrod,2,3 Charles M Cleland,1 Zeyuan Qiu,4 Amber A Guth,2,3 Robin Kleinman,2 Joan Scagliola,2 Judith Haber1 1College of Nursing, New York University, 2Department of Surgery, NYU School of Medicine, 3NYU Clinical Cancer Center, New York, NY, 4Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ, USA Abstract: Breast cancer-related lymphedema is a syndrome of abnormal swelling coupled with multiple symptoms resulting from obstruction or disruption of the lymphatic system associated with cancer treatment. Research has demonstrated that with increased number of symptoms reported, breast cancer survivors' limb volume increased. Lymphedema symptoms in the affected limb may indicate a latent stage of lymphedema in which changes cannot be detected by objective measures. The latent stage of lymphedema may exist months or years before overt swelling occurs. Symptom report may play an important role in detecting lymphedema in clinical practice. The purposes of this study were to: 1 examine the validity, sensitivity, and specificity of symptoms for detecting breast cancer-related lymphedema and 2 determine the best clinical cutoff point for the count of symptoms that maximized the sum of sensitivity and specificity. Data were collected from 250 women, including healthy female adults, breast cancer survivors with lymphedema, and those at risk for lymphedema. Lymphedema symptoms were assessed using a reliable and valid instrument. Validity, sensitivity, and specificity were evaluated using logistic regression, analysis of variance, and areas under receiver operating characteristic curves. Count of lymphedema symptoms was able to differentiate healthy adults from breast cancer survivors with lymphedema and those at risk for lymphedema. A diagnostic cutoff of three symptoms discriminated breast cancer survivors with lymphedema from healthy women with a sensitivity of 94% and a specificity of 97

  1. Cancer related fatigue: implementing guidelines for optimal management.

    Science.gov (United States)

    Pearson, Elizabeth J M; Morris, Meg E; McKinstry, Carol E

    2017-07-18

    Cancer-related fatigue (CRF) is a key concern for people living with cancer and can impair physical functioning and activities of daily living. Evidence-based guidelines for CRF are available, yet inconsistently implemented globally. This study aimed to identify barriers and enablers to applying a cancer fatigue guideline and to derive implementation strategies. A mixed-method study explored the feasibility of implementing the CRF guideline developed by the Canadian Association for Psychosocial Oncology (CAPO). Health professionals, managers and consumers from different practice settings participated in a modified Delphi study with two survey rounds. A reference group informed the design of the study including the surveys. The first round focused on guideline characteristics, compatibility with current practice and experience, and behaviour change. The second survey built upon and triangulated the first round. Forty-five health practitioners and managers, and 68 cancer survivors completed the surveys. More than 75% of participants endorsed the CAPO cancer related fatigue guidelines. Some respondents perceived a lack of resources for accessible and expert fatigue management services. Further barriers to guideline implementation included complexity, limited practical details for some elements, and lack of clinical tools such as assessment tools or patient education materials. Recommendations to enhance guideline applicability centred around four main themes: (1) balancing the level of detail in the CAPO guideline with ease of use, (2) defining roles of different professional disciplines in CRF management, (3) how best to integrate CRF management into policy and practice, (4) how best to ensure a consumer-focused approach to CRF management. Translating current knowledge on optimal management of CRF into clinical practice can be enhanced by the adoption of valid guidelines. This study indicates that it is feasible to adopt the CAPO guidelines. Clinical application may

  2. Altered resting brain connectivity in persistent cancer related fatigue

    Directory of Open Access Journals (Sweden)

    Johnson P. Hampson

    2015-01-01

    Full Text Available There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI. Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected. This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52 and poor sleep quality (P = 0.04, r = 0.52 in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected. Mental fatigue scores were associated with greater default mode network (DMN connectivity to the superior frontal gyrus (P = 0.05 FDR corrected among fatigued subjects (r = 0.82 and less connectivity in the non-fatigued group (r = −0.88. These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent

  3. N- and O-glycosylation Analysis of Human C1-inhibitor Reveals Extensive Mucin-type O-Glycosylation.

    Science.gov (United States)

    Stavenhagen, Kathrin; Kayili, H Mehmet; Holst, Stephanie; Koeleman, Carolien A M; Engel, Ruchira; Wouters, Diana; Zeerleder, Sacha; Salih, Bekir; Wuhrer, Manfred

    2018-06-01

    Human C1-inhibitor (C1-Inh) is a serine protease inhibitor and the major regulator of the contact activation pathway as well as the classical and lectin complement pathways. It is known to be a highly glycosylated plasma glycoprotein. However, both the structural features and biological role of C1-Inh glycosylation are largely unknown. Here, we performed for the first time an in-depth site-specific N - and O -glycosylation analysis of C1-Inh combining various mass spectrometric approaches, including C18-porous graphitized carbon (PGC)-LC-ESI-QTOF-MS/MS applying stepping-energy collision-induced dissociation (CID) and electron-transfer dissociation (ETD). Various proteases were applied, partly in combination with PNGase F and exoglycosidase treatment, in order to analyze the (glyco)peptides. The analysis revealed an extensively O -glycosylated N-terminal region. Five novel and five known O -glycosylation sites were identified, carrying mainly core1-type O -glycans. In addition, we detected a heavily O -glycosylated portion spanning from Thr 82 -Ser 121 with up to 16 O -glycans attached. Likewise, all known six N -glycosylation sites were covered and confirmed by this site-specific glycosylation analysis. The glycoforms were in accordance with results on released N -glycans by MALDI-TOF/TOF-MS/MS. The comprehensive characterization of C1-Inh glycosylation described in this study will form the basis for further functional studies on the role of these glycan modifications. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. 9-Valent HPV vaccine for cancers, pre-cancers and genital warts related to HPV.

    Science.gov (United States)

    Pitisuttithum, Punnee; Velicer, Christine; Luxembourg, Alain

    2015-01-01

    Human papillomavirus (HPV) is the causative agent of nearly all cervical cancer cases as well as a substantial proportion of anal, vulvar, vaginal, penile and oropharyngeal cancers, making it responsible for approximately 5% of the global cancer burden. The first-generation HPV vaccines that is, quadrivalent HPV type 6/11/16/18 vaccine and bivalent HPV type 16/18 vaccine were licensed in 2006 and 2007, respectively. A second-generation 9-valent HPV type 6/11/16/18/31/33/45/52/58 vaccine with broader cancer coverage was initiated even before the first vaccines were approved. By preventing HPV infection and disease due to HPV31/33/45/52/58, the 9vHPV vaccine has the potential to increase prevention of cervical cancer from 70 to 90%. In addition, the 9vHPV vaccine has the potential to prevent 85-95% of HPV-related vulvar, vaginal and anal cancers. Overall, the 9vHPV vaccine addresses a significant unmet medical need, although further health economics and implementation research is needed.

  5. General N-and O-Linked Glycosylation of Lipoproteins in Mycoplasmas and Role of Exogenous Oligosaccharide.

    Science.gov (United States)

    Daubenspeck, James M; Jordan, David S; Simmons, Warren; Renfrow, Matthew B; Dybvig, Kevin

    2015-01-01

    The lack of a cell wall, flagella, fimbria, and other extracellular appendages and the possession of only a single membrane render the mycoplasmas structurally simplistic and ideal model organisms for the study of glycoconjugates. Most species have genomes of about 800 kb and code for few proteins predicted to have a role in glycobiology. The murine pathogens Mycoplasma arthritidis and Mycoplasma pulmonis have only a single gene annotated as coding for a glycosyltransferase but synthesize glycolipid, polysaccharide and glycoproteins. Previously, it was shown that M. arthritidis glycosylated surface lipoproteins through O-linkage. In the current study, O-linked glycoproteins were similarly found in M. pulmonis and both species of mycoplasma were found to also possess N-linked glycans at residues of asparagine and glutamine. Protein glycosylation occurred at numerous sites on surface-exposed lipoproteins with no apparent amino acid sequence specificity. The lipoproteins of Mycoplasma pneumoniae also are glycosylated. Glycosylation was dependent on the glycosidic linkages from host oligosaccharides. As far as we are aware, N-linked glycoproteins have not been previously described in Gram-positive bacteria, the organisms to which the mycoplasmas are phylogenetically related. The findings indicate that the mycoplasma cell surface is heavily glycosylated with implications for the modulation of mycoplasma-host interactions.

  6. Catechol-O-methyltransferase genotype modulates cancer treatment-related cognitive deficits in breast cancer survivors.

    Science.gov (United States)

    Small, Brent J; Rawson, Kerri Sharp; Walsh, Erin; Jim, Heather S L; Hughes, Tiffany F; Iser, Lindsay; Andrykowski, Michael A; Jacobsen, Paul B

    2011-04-01

    Recent attention has focused on the negative effects of chemotherapy on the cognitive performance of cancer survivors. The current study examined modification of this risk by catechol-O-methyltransferase (COMT) genotype based on evidence in adult populations that the presence of a Val allele is associated with poorer cognitive performance. Breast cancer survivors treated with radiotherapy (n = 58), and/or chemotherapy (n = 72), and 204 healthy controls (HCs) completed tests of cognitive performance and provided saliva for COMT genotyping. COMT genotype was divided into Val carriers (Val+; Val/Val, Val/Met) or COMT-Met homozygote carriers (Met; Met/Met). COMT-Val+ carriers performed more poorly on tests of attention, verbal fluency, and motor speed relative to COMT-Met homozygotes. Moreover, COMT-Val+ carriers treated with chemotherapy performed more poorly on tests of attention relative to HC group members who were also Val+ carriers. The results suggest that persons treated with chemotherapy for breast cancer who also possess the COMT-Val gene are susceptible to negative effects on their cognitive health. This research is important because it strives to understand the factors that predispose some cancer survivors to more negative quality-of-life outcomes. Copyright © 2010 American Cancer Society.

  7. Glycosylation in HIV-1 envelope glycoprotein and its biological implications

    KAUST Repository

    Ho, Yung Shwen; Saksena, Nitin K.

    2013-01-01

    architecture, also controls intra- and inter-clade genetic variations. Discerning intra- and inter-clade glycosylation variations could therefore yield important information for understanding the molecular and biological differences between HIV clades and may

  8. [The role of protein glycosylation in immune system].

    Science.gov (United States)

    Ząbczyńska, Marta; Pocheć, Ewa

    2015-01-01

    Glycosylation is one of the most frequent post-translational modifications of proteins. The majority of cell surface and secreted proteins involved in immune response is glycosylated. The structural diversity of glycans depends on monosaccharide composition, type of glycosidic linkage and branching. These structural modifications determine a great variability of glycoproteins. The oligosaccharide components of proteins are regulated mostly by expression of glycosyltransferases and glycosidases and many environmental factors. Glycosylation influences the function of all immune cells. Glycans play a crucial role in intercellular contacts and leukocytes migration. These interactions are important in activation and proliferation of leukocytes and during immune response. The key immune proteins, such as TCR, MHC, TLR and antibodies are glycosylated. Sugars on the surface of pathogens and self-surface glycoproteins are recognized by special carbohydrate binding proteins called lectins. Changes of glycan structure are common in many pathological processes occurring in immune system, therefore they are used as molecular markers of different diseases.

  9. Enzymatic Glycosylation of Small Molecules: Challenging Substrates Require Tailored Catalysts

    Czech Academy of Sciences Publication Activity Database

    Desmet, T.; Soetaert, W.; Bojarová, Pavla; Křen, Vladimír; Dijkhuizen, L.; Eastwick-Field, V.; Schiller, A.

    2012-01-01

    Roč. 18, č. 35 (2012), s. 10786-10801 ISSN 0947-6539 Institutional support: RVO:61388971 Keywords : acceptor specificity * enzyme engineering * glycosylation Subject RIV: CE - Biochemistry Impact factor: 5.831, year: 2012

  10. IN VITRO STUDY ON INHIBITION OF GLYCOSYLATION OF ...

    African Journals Online (AJOL)

    Administrator

    complications of diabetes mellitus (Makita et al., 1991). Apart from protein ... enzymes; inhibition of regulatory molecule binding; crosslinking of glycosylated .... further investigation specific bio active compound responsible for such activities.

  11. Exploratory study of impact of cancer-related posttraumatic stress symptoms on diabetes self-management among cancer survivors.

    Science.gov (United States)

    James, Janey; Harris, Yael T; Kronish, Ian M; Wisnivesky, Juan P; Lin, Jenny J

    2018-02-01

    Posttraumatic stress symptoms (PTSS) can be triggered by a diagnosis of a potentially life-threatening illness such as cancer. Little is known about the impact of cancer-related PTSS symptoms on self-management behaviors for comorbid chronic medical conditions such as diabetes mellitus (DM). We recruited patients with DM and a recent diagnosis of early-stage cancer from 2 medical centers in New York City. Cancer-related PTSS were assessed using the Impact of Events Scale (score ≥ 26). DM self-management behaviors (medication adherence, exercise, healthy diet, and glucose testing) were measured 3 months later. Logistic regression was used to assess the association between cancer-related PTSS symptoms and DM self-management behaviors, adjusting for gender, marital status, and anxiety symptoms. Of 56 participants recruited, 33% reported cancer-related PTSS symptoms. Elevated cancer-related PTSS symptoms were associated with lack of healthy diet (odds ratio: 0.08, 95% confidence interval: 0.01-0.62). Early-stage cancer survivors with cancer-related PTSS symptoms were less likely to adhere to some DM self-management behaviors. Providers should recognize the impact of cancer-related PTSS symptoms to better support comorbid disease management in cancer survivors. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylated variants of a single polypeptide chain.

    OpenAIRE

    Murphy, P A; Cebula, T A; Windle, B E

    1981-01-01

    Rabbit endogenous pyrogens were of about the same molecular size, but showed considerable heterogeneity of their isoelectric points. We attempted to show that this heterogeneity was attributable to variable glycosylation of a single polypeptide chain. When peritoneal exudate cells were stimulated to make pyrogens in the presence of 2-deoxy-D-glucose, there was a relatively trivial suppression of pyrogen release, and analysis by isoelectric focusing showed parallel inhibition of secretion of a...

  13. Cancer-Related Fatigue in Adolescents and Young Adults After Cancer Treatment: Persistent and Poorly Managed.

    Science.gov (United States)

    Spathis, Anna; Hatcher, Helen; Booth, Sara; Gibson, Faith; Stone, Paddy; Abbas, Laura; Barclay, Matt; Brimicombe, James; Thiemann, Pia; McCabe, Martin G; Campsey, Rachel; Hooker, Louise; Moss, Wendy; Robson, Jane; Barclay, Stephen

    2017-09-01

    Cancer-related fatigue is the most prevalent and distressing symptom experienced by adolescents and young adults (AYAs). An electronic survey was undertaken to ascertain current fatigue management and perceptions of its effectiveness. Eighty-five percent of responders (68/80) experienced fatigue, and it was worse more than 1 year after cancer treatment ended, compared to fatigue management. Although advice to exercise was the most frequent intervention, the greatest impact of fatigue was on the ability to exercise and most did not find exercise advice helpful. Early intervention is warranted, supporting AYAs to persevere with increasing activity.

  14. Adherence to Guidelines for Cancer Survivors and Health-Related Quality of Life among Korean Breast Cancer Survivors

    Directory of Open Access Journals (Sweden)

    Sihan Song

    2015-12-01

    Full Text Available There is limited evidence on the association between adherence to guidelines for cancer survivors and health-related quality of life (HRQoL. In a cross-sectional study of Korean breast cancer survivors, we examined whether adherence to the guidelines of the American Cancer Society (ACS and World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR for cancer survivors was related to levels of HRQoL, assessed by the Korean version of Core 30 (C30 and Breast cancer module 23 (BR23 of the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire (EORTC-QLQ. We included a total of 160 women aged 21 to 79 years who had been diagnosed with breast cancer according to American Joint Committee on Cancer (AJCC stages I to III and had breast cancer surgery at least six months before the interview. Increasing adherence to ACS guidelines was associated with higher scores of social functioning (p for trend = 0.05, whereas increasing adherence to WCRF/AICR recommendations was associated with higher scores of arm symptoms (p for trend = 0.01. These associations were limited to those with stage II or III cancer. Diet may be an important factor in relation to quality of life among Korean breast cancer survivors, however our findings warrant further prospective studies to evaluate whether healthy diet improves survivors’ quality of life.

  15. Cancer-related aspects of regeneration research: a review

    International Nuclear Information System (INIS)

    Donaldson, D.J.; Mason, J.M.

    1975-01-01

    Tissue regeneration is simply the replacement of lost cells of a tissue by those remaining. Epimorphic regeneration involves dedifferentiation of many tissues and their organization into a blastema which eventually differentiates into the missing part, usually an appendage. A detailed comparison of the cell membrane changes occurring in epimorphic regeneration, tissue regeneration and cancer can contribute to greater understanding of the differences between normal and tumor cells. Further, there is evidence that epimorphic regeneration fields may in some instances suppress tumor induction and control existing tumors. This influence may be mediated by bioelectric fields, which are ubiquitous in nature and appear to control many cellular events. Disruption of these bioelectric fields suppresses epimorphic regeneration and may lead to cancer in mammals, while applied electric fields alter regenerative events and cause tumor regression. Studies on x-radioinduced regeneration suppression in relation to mutagenesis are also reviewed

  16. Wood-related occupations, wood dust exposure, and sinonasal cancer.

    Science.gov (United States)

    Hayes, R B; Gerin, M; Raatgever, J W; de Bruyn, A

    1986-10-01

    A case-control study was conducted to examine the relations between type of woodworking and the extent of wood dust exposure to the risks for specific histologic types of sinonasal cancer. In cooperation with the major treatment centers in the Netherlands, 116 male patients newly diagnosed between 1978 and 1981 with primary malignancies of epithelial origin of this site were identified for study. Living controls were selected from the municipal registries, and deceased controls were selected from the national death registry. Interviews were completed for 91 (78%) cases and 195 (75%) controls. Job histories were coded by industry and occupation. An index of exposure was developed to classify the extent of occupational exposure to wood dust. When necessary, adjustment was made for age and usual cigarette use. The risk for nasal adenocarcinoma was elevated by industry for the wood and paper industry (odds ratio (OR) = 11.9) and by occupation for those employed in furniture and cabinet making (OR = 139.8), in factory joinery and carpentry work (OR = 16.3), and in association with high-level wood dust exposure (OR = 26.3). Other types of nasal cancer were not found to be associated with wood-related industries or occupations. A moderate excess in risk for squamous cell cancer (OR = 2.5) was associated with low-level wood dust exposure; however, no dose-response relation was evident. The association between wood dust and adenocarcinoma was strongest for those employed in wood dust-related occupations between 1930 and 1941. The risk of adenocarcinoma did not appear to decrease for at least 15 years after termination of exposure to wood dust. No cases of nasal adenocarcinoma were observed in men whose first exposure to wood dust occurred after 1941.

  17. Molecular Basis of Alcohol-Related Gastric and Colon Cancer.

    Science.gov (United States)

    Na, Hye-Kyung; Lee, Ja Young

    2017-05-24

    Many meta-analysis, large cohort studies, and experimental studies suggest that chronic alcohol consumption increases the risk of gastric and colon cancer. Ethanol is metabolized by alcohol dehydrogenases (ADH), catalase or cytochrome P450 2E1 (CYP2E1) to acetaldehyde, which is then further oxidized to acetate by aldehyde dehydrogenase (ALDH). Acetaldehyde has been classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen to humans. The acetaldehyde level in the stomach and colon is locally influenced by gastric colonization by Helicobacter pylori or colonic microbes, as well as polymorphisms in the genes encoding tissue alcohol metabolizing enzymes, especially ALDH2. Alcohol stimulates the uptake of carcinogens and their metabolism and also changes the composition of enteric microbes in a way to enhance the aldehyde level. Alcohol also undergoes chemical coupling to membrane phospholipids and disrupts organization of tight junctions, leading to nuclear translocation of β-catenin and ZONAB, which may contributes to regulation of genes involved in proliferation, invasion and metastasis. Alcohol also generates reactive oxygen species (ROS) by suppressing the expression of antioxidant and cytoprotective enzymes and inducing expression of CYP2E1 which contribute to the metabolic activation of chemical carcinogens. Besides exerting genotoxic effects by directly damaging DNA, ROS can activates signaling molecules involved in inflammation, metastasis and angiogenesis. In addition, alcohol consumption induces folate deficiency, which may result in aberrant DNA methylation profiles, thereby influencing cancer-related gene expression.

  18. Central venous catheter-related bloodstream infections in cancer patients

    International Nuclear Information System (INIS)

    Butt, T.; Afzal, R.K.; Ahmad, R.N.; Hussain, I.; Anwar, M.

    2004-01-01

    Objective: To determine the frequency of central venous catheter-related bloodstream infections (CR-BSI) in cancer patients and the antimicrobial susceptibility pattern of the isolates. Subjects and Methods: Cancer patients requiring short or long-term central venous catheterization at the time of admission or thereafter were included. Catheter tips on removal were cultured quantitatively; specimens of blood and pus were cultured qualitatively. Isolates were identified and antimicrobial susceptibility testing was performed by standard techniques. Results: Eighty-nine patients were included in the study. The frequency of CR-BSI was 17%. Out of the 19 organisms isolated, 10 (53%) were Gram-positive cocci, 8 (42%) were Gram-negative rods and 1 (5%) was a fungus. Coagulase negative staphylococci (27%) were the predominant pathogens. Among the staphylococci, 46% of the isolates were methicillin-resistant. All Gram-positive isolates were susceptive to glycopeptides. Gram-negative rods were resistant to most of the commonly used antimicrobial groups. Conclusion: Central venous catheter is an important source of bloodstream infections in cancer patients. Most of the infections are caused by Gram-positive cocci. Rigorous infection control measures and continuous surveillance is required to curb the frequency of these infections. (author)

  19. Cancer-related communication, relationship intimacy, and psychological distress among couples coping with localized prostate cancer.

    Science.gov (United States)

    Manne, Sharon; Badr, Hoda; Zaider, Talia; Nelson, Christian; Kissane, David

    2010-03-01

    The present study evaluated intimacy as a mechanism for the effects of relationship-enhancing (self-disclosure, mutual constructive communication) and relationship-compromising communication (holding back, mutual avoidance, and demand-withdraw communication) on couples' psychological distress. Seventy-five men diagnosed with localized prostate cancer in the past year and their partners completed surveys about communication, intimacy, and distress. Multi-level models with the couple as unit of analyses indicated that the association between mutual constructive communication, mutual avoidance, and patient demand-partner withdraw and distress could be accounted for by their influence on relationship intimacy. Intimacy did not mediate associations between self-disclosure, holding back, and partner demand-patient withdraw communication and distress. These findings indicate that the way in which couples talk about cancer-related concerns as well as the degree to which one or both partners avoid talking about cancer-related concerns can either facilitate or reduce relationship intimacy, and that it is largely by this mechanism that these three communication strategies impact psychological distress. Relationship intimacy and how patients and partners communicate to achieve this intimacy is important for the psychological adjustment of early stage prostate cancer survivors and their partners.

  20. Lower heart rate variability is associated with cancer-related fatigue in breast cancer survivors

    Directory of Open Access Journals (Sweden)

    Alexandra Dupont

    2012-09-01

    Full Text Available Background : Fatigue is the most common and distressing symptom reported by breast cancer survivors and yet the pathophysiology of cancer-related fatigue remains largely unknown. Fatigue is associated with lower parasympathetic and higher sympathetic nervous system activity in non-cancer samples, but only one study has demonstrated this same relationship in breast cancer survivors. This study evaluates the relationship between fatigue and basal autonomic nervous system activity as measured by heart rate variability (HRV in a sample of breast cancer survivors. Methods : Women who had been diagnosed with early stage breast cancer before the age of 50 were recruited from the UCLA tumor registry and completed psychological questionnaires, including measures of fatigue. A subset of these women (n=30 participated in a follow-up study in which they completed measures of fatigue, energy and mood four times per day for 5 days using electronic diaries, provided 3 days of saliva samples for cortisol assessment and underwent physiological assessment including electrocardiogram (ECG. HRV was assessed via ECG R-R wave spectral and time sequence analysis. Results : Questionnaire measures of fatigue were negatively associated with indices of parasympathetic nervous system activity, B= − 3.85, p = 0.04 for RMSSD (root of the mean squared difference of successive normal to normal waves and B= − 76.97, p = 0.04 for LF power % (low-frequency wave power percentage. Daily fatigue was also associated with lower basal HRV, B= − 15.1, p = 0.04 for RMSSD. However, fatigue indices were not associated with sympathetic nervous system activity as measured by low- to high-frequency wave ratio. Of note, fatigue was not associated with average daily cortisol output (AUC. Conclusions : Lower HRV has been associated with increased chronic inflammation, which is elevated in cancer survivors reporting persistent fatigue, thus providing insight into

  1. Effects of yoga on cancer-related fatigue and global side-effect burden in older cancer survivors.

    Science.gov (United States)

    Sprod, Lisa K; Fernandez, Isabel D; Janelsins, Michelle C; Peppone, Luke J; Atkins, James N; Giguere, Jeffrey; Block, Robert; Mustian, Karen M

    2015-01-01

    Sixty percent of cancer survivors are 65years of age or older. Cancer and its treatments lead to cancer-related fatigue and many other side effects, in turn, creating substantial global side-effect burden (total burden from all side effects) which, ultimately, compromises functional independence and quality of life. Various modes of exercise, such as yoga, reduce cancer-related fatigue and global side-effect burden in younger cancer survivors, but no studies have specifically examined the effects of yoga on older cancer survivors. The purpose of this study was to assess the effects of a 4-week yoga intervention (Yoga for Cancer Survivors: YOCAS©®) on overall cancer-related fatigue, and due to its multidimensional nature, the subdomains of cancer-related fatigue (general, physical, emotional, and mental) and global side-effect burden in older cancer survivors. We conducted a secondary analysis on data from a multicenter phase III randomized controlled clinical trial with 2 arms (standard care and standard care plus a 4-week YOCAS©® intervention). The sample for this secondary analysis was 97 older cancer survivors (≥60years of age), between 2months and 2years post-treatment, who participated in the original trial. Participants in the YOCAS©® intervention arm reported significantly lower cancer-related fatigue, physical fatigue, mental fatigue, and global side-effect burden than participants in the standard care arm following the 4-week intervention period (peffective standardized yoga intervention for reducing cancer-related fatigue, physical fatigue, mental fatigue, and global side-effect burden among older cancer survivors. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Spinal cord stimulation for cancer-related pain in adults.

    Science.gov (United States)

    Peng, Lihua; Min, Su; Zejun, Zhou; Wei, Ke; Bennett, Michael I

    2015-06-29

    This is an update of a review first published in The Cochrane Library in Issue 3, 2013. Cancer-related pain places a heavy burden on public health with related high expenditure. Severe pain is associated with a decreased quality of life in patients with cancer. A significant proportion of patients with cancer-related pain are under-treated. There is a need for more effective control of cancer-related pain. Spinal cord stimulation (SCS) may have a role in pain management. The effectiveness and safety of SCS for patients with cancer-related pain is currently unknown. This systematic review evaluated the effectiveness of SCS for cancer-related pain compared with standard care using conventional analgesic medication. We also appraised risk and potential adverse events associated with the use of SCS. This is an update of a review first published in The Cochrane Library in Issue 3, 2013. The search strategy for the update was the same as in the original review. We searched the following bibliographic databases in order to identify relevant studies: the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library; MEDLINE; EMBASE; and CBM (Chinese Biomedical Database) in October 2014. We also handsearched relevant journals. There were no language restrictions. We planned to include randomised controlled trials (RCTs) that directly compared SCS with other interventions with regards to the effectiveness of pain management. We also planned to include cross-over trials that compared SCS with another treatment. We planned to identify non-randomised controlled trials but these would only be included if no RCTs could be found. The literature search for the update of this review found 121 potentially eligible articles. The initial search strategy yielded 430 articles. By scrutinising titles and abstracts, we found 412 articles irrelevant to the analytical purpose of this systematic review due to different scopes of diseases or different methods of intervention

  3. Systems analysis of singly and multiply O-glycosylated peptides in the human serum glycoproteome via EThcD and HCD mass spectrometry.

    Science.gov (United States)

    Zhang, Yong; Xie, Xinfang; Zhao, Xinyuan; Tian, Fang; Lv, Jicheng; Ying, Wantao; Qian, Xiaohong

    2018-01-06

    Human serum has been intensively studied to identify biomarkers via global proteomic analysis. The altered O-glycoproteome is associated with human pathological state including cancer, inflammatory and degenerative diseases and is an attractive source of disease biomarkers. Because of the microheterogeneity and macroheterogeneity of O-glycosylation, site-specific O-glycosylation analysis in human serum is still challenging. Here, we developed a systematic strategy that combined multiple enzyme digestion, multidimensional separation for sample preparation and high-resolution tandem MS with Byonic software for intact O-glycopeptide characterization. We demonstrated that multiple enzyme digestion or multidimensional separation can make sample preparation more efficient and that EThcD is not only suitable for the identification of singly O-glycosylated peptides (50.3%) but also doubly (21.2%) and triply (28.5%) O-glycosylated peptides. Totally, with the strict scoring criteria, 499 non-redundant intact O-glycopeptides, 173 O-glycosylation sites and 6 types of O-glycans originating from 49 O-glycoprotein groups were identified in human serum, including 121 novel O-glycosylation sites. Currently, this is the largest data set of site-specific native O-glycoproteome from human serum samples. We expect that the strategies developed by this study will facilitate in-depth analyses of native O-glycoproteomes in human serum and provide opportunities to understand the functional roles of protein O-glycosylation in human health and diseases. The altered O-glycoproteome is associated with human pathological state and is an attractive source of disease biomarkers. However, site-specific O-glycosylation analysis is challenging because of the microheterogeneity (different glycoforms attached to one glycosylation site) and macroheterogeneity (site occupancy) of O-glycosylation. In this work, we developed a systematic strategy for intact O-glycopeptide characterization. This study took

  4. [Non-enzymatic glycosylation of dietary protein in vitro].

    Science.gov (United States)

    Bednykh, B S; Evdokimov, I A; Sokolov, A I

    2015-01-01

    Non-enzymatic glycosylation of proteins, based on discovered by Mayarn reaction of carbohydrate aldehyde group with a free amino group of a protein molecule, is well known to experts in biochemistry of food industry. Generated brown solid in some cases give the product marketable qualities--crackling bread--in others conversely, worsen the product. The biological effects of far-advanced products of non-enzymatic protein glycosylation reaction have not been studied enough, although it was reported previously that they are not split by digestive enzymes and couldn't be absorbed by animals. The objective of this work was to compare the depth of glycosylation of different food proteins of animal and vegetable origin. The objects of the study were proteins of animal (casein, lactoglobulin, albumin) and vegetable (soy isolate, proteins of rice flour, buckwheat, oatmeal) origin, glucose and fructose were selected as glycosylation agents, exposure 15 days at 37 degrees C. Lactoglobulin was glycosylated to a lesser extent among the proteins of animal origin while protein of oatmeal was glycosylated in the least degree among vegetable proteins. Conversely, such proteins as casein and soya isolate protein bound rather large amounts of carbohydrates. Fructose binding with protein was generally higher than the binding of glucose. The only exception was a protein of oatmeal. When of glucose and fructose simultaneously presented in the incubation medium, glucose binding usually increased while binding of fructose, in contrast, reduced. According to the total amount of carbohydrate (mcg), which is able to attach a protein (mg) the studied food proteins located in the following order: albumin (38) > soy protein isolate (23) > casein (15,) > whey protein rice flour protein (6) > protein from buckwheat flour (3) > globulin (2) > protein of oatmeal (0.3). The results obtained are to be used to select the optimal combination of proteins and carbohydrates, in which the glycosylation

  5. Is there an increased risk of cancer among spouses of patients with an HPV-related cancer: A systematic review.

    Science.gov (United States)

    Mirghani, Haitham; Sturgis, Erich M; Aupérin, Anne; Monsonego, Joseph; Blanchard, Pierre

    2017-04-01

    High-risk human papillomaviruses (HR-HPV) are the cause of most ano-genital cancers and a fast growing subset of oropharyngeal cancer. As these malignancies occur as a result of an HPV- infection transmitted through intimate contact, many patients with HPV- induced cancer and their partners are concerned about HPV-transmission and the potential partners' cancer risk. Few studies have addressed this issue and whether the HPV-related cancer risk of partners of patients with HPV-related cancers is comparable to or greater than that of the general population. We performed a systematic review of the published literature addressing this issue. Out of 1055 references screened, 53 articles were found eligible for inclusion. Regarding the issue of coincidence of HPV-induced oropharyngeal and/or anogenital cancers in couples, 13 case-reports or case-series were reported and 9 larger studies based on population-registries. Four of these registry studies showed an increased risk of cervical cancer in the partner while four did not. Among the four positive studies, odds ratios for the development of HPV-related cancer among spouses were between 2.6 and 6.7. One study showed an increased risk of tongue or tonsil cancer among husbands of women with cervical dysplasia or cancer. Overall the absolute risk increase in all these studies was small, on the order of 1-3%, although potentially underestimated. Indeed, all these studies have assessed partner's cancer risk at only one anatomical site whereas HPV- related malignancies can affect different locations. This systematic review suggests a small trend of increase risk in HPV-associated cancers among spouses of patients with HPV-related cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Healing environments in cancer treatment and care. Relations of space and practice in hematological cancer treatment

    DEFF Research Database (Denmark)

    Høybye, Mette Terp

    2013-01-01

    of the individual patient ’ s needs, values and experiences is key to developing the environment to support the patient quality of life. The present study holds implications for practice to inform design of future hospital environments for cancer treatment. The study points to the importance for being attentive...... these concepts, the study demonstrates how the hospital environment is a fl ow of relations between space and practice that changes and challenges a structural idea of design and healing. Patients ’ sense of healing changes with the experience of progression in treatment and the capacity of the hospital space...... to incite an experience of homeliness and care. Furthermore, cancer patients continuously challenge the use and limits of space by individual objects and practices of privacy and home. Discussion. Healing environments are complex relations between practices, space and care, where recognition...

  7. Risk of treatment-related esophageal cancer among breast cancer survivors

    DEFF Research Database (Denmark)

    Morton, L M; Gilbert, E S; Hall, P

    2012-01-01

    Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use.......Radiotherapy for breast cancer may expose the esophagus to ionizing radiation, but no study has evaluated esophageal cancer risk after breast cancer associated with radiation dose or systemic therapy use....

  8. Relation of erythrocyte and iron indices to oral cancer growth

    International Nuclear Information System (INIS)

    Bhattathiri, Vasudevaru Narayanan

    2001-01-01

    Background and purpose: Anaemia is known to influence prognosis of head and neck cancer patients, but how anaemia and tumour growth influences each other is not clear. The present study investigates the relation of erythrocyte and iron indices of oral cancer patients to primary tumour size (Tsize), invasiveness and lymph node involvement. Materials and methods: The haemoglobin (Hb), erythrocyte count (RBC), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), Serum iron (SFe), transferrin iron-binding capacity (TIBC) and transferrin saturation (%Fe) were evaluated in 217 untreated patients with epidermoid cancer of the bucco-gingivo-palatine area. The association of erythrocyte and iron indices with sex, tumour size groups, invasion of adjacent structures and lymph node involvement, as well as the relation of SFe to Hb were analyzed. Results: Most of the patients were anaemic in terms of Hb (63%), RBC (43%) and PCV (48.4%) but almost all had normal or higher MCH (97.3%) and MCV (93.3%) though MCHC was less than normal in 70.7%. Normal or higher SFe was seen in nearly 70% and TIBC in 45% of patients. Hb, RBC and PCV were significantly lower in women, but there was no difference between men and women in the case of MCV, MCH and MCHC. Primary tumour size showed negative association with Hb, RBC and PCV but positive association with MCH ( 4 cm: 31. 7 pg; P=0.04) and MCHC ( 4 cm: 32.1; P=0.006). MCV, SFe, TIBC and %Fe did not show any relation to primary tumour size. None of the indices had any relation to invasion of adjacent structures or lymph node involvement. MCH, MCHC and MCV were not different in men and women but women had significantly lower Hb, RBC and PCV. The SFe showed poor correlation with Hb. Conclusions: The negative association of Hb, RBC and PCV with tumour size is most likely due to chronic RBC destruction, probably tumour induced, with the products of

  9. Traditional Chinese medical comprehensive therapy for cancer-related fatigue.

    Science.gov (United States)

    Yang, Lu; Li, Tian-Tian; Chu, Yu-Ting; Chen, Ke; Tian, Shao-Dan; Chen, Xin-Yi; Yang, Guo-Wang

    2016-01-01

    Cancer-related fatigue (CRF) is a common and one of the most severe symptom in the period of onset, diagnosis, treatment and rehabilitation process of cancer. But there are no confirmed measures to relieve this problem at present. Traditional Chinese medical comprehensive therapy has its advantages in dealing with this condition. Based on the research status of CRF, the following problems have been analyzed and solved: the term of CRF has been defined and recommended, and the definition has been made clear; the disease mechanism is proposed, i.e. healthy qi has been impaired in the long-term disease duration, in the process of surgery, chemotherapy, radiotherapy and biology disturbing; it is clear that the clinical manifestations are related to six Chinese medicine patterns: decreased functioning of the Pi (Spleen) and Wei (Stomach), deficiency of the Pi with dampness retention, deficiency of the Xin (Heart) and Pi, disharmony between the Gan (Liver) and Pi, deficiency of the Pi and Shen (Kidney), and deficiency of the Fei (Lung) and Shen. Based on its severity, the mild patients are advised to have non-drug psychological intervention and sleep treatment in cooperation with appropriate exercise; diet therapy are recommended to moderate patients together with sleep treatment and acupuncture, severe patients are recommended to have herbal treatment based on pattern differentiation together with physiological sleep therapy.

  10. Characterization of transformation related genes in oral cancer cells.

    Science.gov (United States)

    Chang, D D; Park, N H; Denny, C T; Nelson, S F; Pe, M

    1998-04-16

    A cDNA representational difference analysis (cDNA-RDA) and an arrayed filter technique were used to characterize transformation-related genes in oral cancer. From an initial comparison of normal oral epithelial cells and a human papilloma virus (HPV)-immortalized oral epithelial cell line, we obtained 384 differentially expressed gene fragments and arrayed them on a filter. Two hundred and twelve redundant clones were identified by three rounds of back hybridization. Sequence analysis of the remaining clones revealed 99 unique clones corresponding to 69 genes. The expression of these transformation related gene fragments in three nontumorigenic HPV-immortalized oral epithelial cell lines and three oral cancer cell lines were simultaneously monitored using a cDNA array hybridization. Although there was a considerable cell line-to-cell line variability in the expression of these clones, a reliable prediction of their expression could be made from the cDNA array hybridization. Our study demonstrates the utility of combining cDNA-RDA and arrayed filters in high-throughput gene expression difference analysis. The differentially expressed genes identified in this study should be informative in studying oral epithelial cell carcinogenesis.

  11. Cancer-Related Post-traumatic Stress (PDQ®)—Patient Version

    Science.gov (United States)

    Cancer-related post-traumatic stress can occur any time from diagnosis to after treatment ends. Shock, fear, helplessness, or horror can be felt by cancer patients and lead to cancer-related post-traumatic stress. Learn about the causes and ways doctors can help manage these symptoms of distress in this expert-reviewed summary.

  12. Evolutionary Pattern of N-Glycosylation Sequon Numbers  in Eukaryotic ABC Protein Superfamilies

    Directory of Open Access Journals (Sweden)

    R. Shyama Prasad Rao

    2010-02-01

    Full Text Available Many proteins contain a large number of NXS/T sequences (where X is any amino acid except proline which are the potential sites of asparagine (N linked glycosylation. However, the patterns of occurrence of these N-glycosylation sequons in related proteins or groups of proteins and their underlying causes have largely been unexplored. We computed the actual and probabilistic occurrence of NXS/T sequons in ABC protein superfamilies from eight diverse eukaryotic organisms. The ABC proteins contained significantly higher NXS/T sequon numbers compared to respective genome-wide average, but the sequon density was significantly lower owing to the increase in protein size and decrease in sequon specific amino acids. However, mammalian ABC proteins have significantly higher sequon density, and both serine and threonine containing sequons (NXS and NXT have been positively selected—against the recent findings of only threonine specific Darwinian selection of sequons in proteins. The occurrence of sequons was positively correlated with the frequency of sequon specific amino acids and negatively correlated with proline and the NPS/T sequences. Further, the NPS/T sequences were significantly higher than expected in plant ABC proteins which have the lowest number of NXS/T sequons. Accord- ingly, compared to overall proteins, N-glycosylation sequons in ABC protein superfamilies have a distinct pattern of occurrence, and the results are discussed in an evolutionary perspective.

  13. Defectively N-glycosylated and non-O-glycosylated aminopeptidase N (CD13) is normally expressed at the cell surface and has full enzymatic activity

    DEFF Research Database (Denmark)

    Norén, K; Hansen, Gert Helge; Clausen, H

    1997-01-01

    In order to study the effects of the absence of O-glycosylation and modifications of N-glycosylation on a class II membrane protein, pig and human aminopeptidase N (CD13) were stably expressed in the ldl(D) cell line. This cell line carries a UDP-Gal/UDP-GalNAc-epimerase deficiency which blocks...... the conversion of glucose into galactose derivatives. Thus it is possible in the ldl(D) cell line to selectively block O-glycosylation by the omission of N-acetylgalactoseamine from the culture medium and to alter N-glycosylation by the omission of galactose. In this way selectively altered glycosylated forms...

  14. In-Depth N-Glycosylation Reveals Species-Specific Modifications and Functions of the Royal Jelly Protein from Western (Apis mellifera) and Eastern Honeybees (Apis cerana).

    Science.gov (United States)

    Feng, Mao; Fang, Yu; Han, Bin; Xu, Xiang; Fan, Pei; Hao, Yue; Qi, Yuping; Hu, Han; Huo, Xinmei; Meng, Lifeng; Wu, Bin; Li, Jianke

    2015-12-04

    Royal jelly (RJ), secreted by honeybee workers, plays diverse roles as nutrients and defense agents for honeybee biology and human health. Despite being reported to be glycoproteins, the glycosylation characterization and functionality of RJ proteins in different honeybee species are largely unknown. An in-depth N-glycoproteome analysis and functional assay of RJ produced by Apis mellifera lingustica (Aml) and Apis cerana cerana (Acc) were conducted. RJ produced by Aml yielded 80 nonredundant N-glycoproteins carrying 190 glycosites, of which 23 novel proteins harboring 35 glycosites were identified. For Acc, all 43 proteins glycosylated at 138 glycosites were reported for the first time. Proteins with distinct N-glycoproteomic characteristics in terms of glycoprotein species, number of N-glycosylated sites, glycosylation motif, abundance level of glycoproteins, and N-glycosites were observed in this two RJ samples. The fact that the low inhibitory efficiency of N-glycosylated major royal jelly protein 2 (MRJP2) against Paenibacillus larvae (P. larvae) and the absence of antibacterial related glycosylated apidaecin, hymenoptaecin, and peritrophic matrix in the Aml RJ compared to Acc reveal the mechanism for why the Aml larvae are susceptible to P. larvae, the causative agent of a fatal brood disease (American foulbrood, AFB). The observed antihypertension activity of N-glycosylated MRJP1 in two RJ samples and a stronger activity found in Acc than in Aml reveal that specific RJ protein and modification are potentially useful for the treatment of hypertensive disease for humans. Our data gain novel understanding that the western and eastern bees have evolved species-specific strategies of glycosylation to fine-tune protein activity for optimizing molecular function as nutrients and immune agents for the good of honeybee and influence on the health promoting activity for human as well. This serves as a valuable resource for the targeted probing of the biological

  15. Functional Analysis of Glycosylation of Zika Virus Envelope Protein.

    Science.gov (United States)

    Fontes-Garfias, Camila R; Shan, Chao; Luo, Huanle; Muruato, Antonio E; Medeiros, Daniele B A; Mays, Elizabeth; Xie, Xuping; Zou, Jing; Roundy, Christopher M; Wakamiya, Maki; Rossi, Shannan L; Wang, Tian; Weaver, Scott C; Shi, Pei-Yong

    2017-10-31

    Zika virus (ZIKV) infection causes devastating congenital abnormities and Guillain-Barré syndrome. The ZIKV envelope (E) protein is responsible for viral entry and represents a major determinant for viral pathogenesis. Like other flaviviruses, the ZIKV E protein is glycosylated at amino acid N154. To study the function of E glycosylation, we generated a recombinant N154Q ZIKV that lacks the E glycosylation and analyzed the mutant virus in mammalian and mosquito hosts. In mouse models, the mutant was attenuated, as evidenced by lower viremia, decreased weight loss, and no mortality; however, knockout of E glycosylation did not significantly affect neurovirulence. Mice immunized with the mutant virus developed a robust neutralizing antibody response and were completely protected from wild-type ZIKV challenge. In mosquitoes, the mutant virus exhibited diminished oral infectivity for the Aedes aegypti vector. Collectively, the results demonstrate that E glycosylation is critical for ZIKV infection of mammalian and mosquito hosts. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. The distribution of lung cancer mortality in Cape Town and related ...

    African Journals Online (AJOL)

    1991-04-20

    Apr 20, 1991 ... In the case of white people demographic as wel! as socio- economic .... correlation analysis,24 were used to identify the cancer-related variables. ..... papers presented at the 24th Annual Symposium of Fundamental Cancer.

  17. The S-Layer Glycoprotein of the Crenarchaeote Sulfolobus acidocaldarius Is Glycosylated at Multiple Sites with Chitobiose-Linked N-Glycans

    Directory of Open Access Journals (Sweden)

    Elham Peyfoon

    2010-01-01

    Full Text Available Glycosylation of the S-layer of the crenarchaea Sulfolobus acidocaldarius has been investigated using glycoproteomic methodologies. The mature protein is predicted to contain 31 N-glycosylation consensus sites with approximately one third being found in the C-terminal domain spanning residues L1004-Q1395. Since this domain is rich in Lys and Arg and therefore relatively tractable to glycoproteomic analysis, this study has focused on mapping its N-glycosylation. Our analysis identified nine of the 11 consensus sequence sites, and all were found to be glycosylated. This constitutes a remarkably high glycosylation density in the C-terminal domain averaging one site for each stretch of 30–40 residues. Each of the glycosylation sites observed was shown to be modified with a heterogeneous family of glycans, with the largest having a composition Glc1Man2GlcNAc2 plus 6-sulfoquinovose (QuiS, consistent with the tribranched hexasaccharide previously reported in the cytochrome b558/566 of S. acidocaldarius. S. acidocaldarius is the only archaeal species whose N-glycans are known to be linked via the chitobiose core disaccharide that characterises the N-linked glycans of Eukarya.

  18. Glycosylation of the self-recognizing Escherichia coli Ag43 autotransporter protein

    DEFF Research Database (Denmark)

    Sherlock, O.; Dobrindt, U.; Jensen, J.B.

    2006-01-01

    a novel member to this exclusive group, namely, antigen 43 (Ag43), a self-recognizing autotransporter protein. By mass spectrometry Ag43 was demonstrated to be glycosylated by addition of heptose residues at several positions in the passenger domain. Glycosylation of Ag43 by the action of the Aah and Tib......C glycosyltransferases was observed in laboratory strains. Importantly, Ag43 was also found to be glycosylated in a wild-type strain, suggesting that Ag43-glycosylation may be a widespread phenomenon. Glycosylation of Ag43 does not seem to interfere with its self-associating properties. However, the glycosylated form...

  19. Site-specific O-glycosylation of members of the low-density lipoprotein receptor superfamily enhances ligand interactions.

    Science.gov (United States)

    Wang, Shengjun; Mao, Yang; Narimatsu, Yoshiki; Ye, Zilu; Tian, Weihua; Goth, Christoffer K; Lira-Navarrete, Erandi; Pedersen, Nis B; Benito-Vicente, Asier; Martin, Cesar; Uribe, Kepa B; Hurtado-Guerrero, Ramon; Christoffersen, Christina; Seidah, Nabil G; Nielsen, Rikke; Christensen, Erik I; Hansen, Lars; Bennett, Eric P; Vakhrushev, Sergey Y; Schjoldager, Katrine T; Clausen, Henrik

    2018-05-11

    The low-density lipoprotein receptor (LDLR) and related receptors are important for the transport of diverse biomolecules across cell membranes and barriers. Their functions are especially relevant for cholesterol homeostasis and diseases, including neurodegenerative and kidney disorders. Members of the LDLR-related protein family share LDLR class A (LA) repeats providing binding properties for lipoproteins and other biomolecules. We previously demonstrated that short linker regions between these LA repeats contain conserved O -glycan sites. Moreover, we found that O -glycan modifications at these sites are selectively controlled by the GalNAc-transferase isoform, GalNAc-T11. However, the effects of GalNAc-T11-mediated O -glycosylation on LDLR and related receptor localization and function are unknown. Here, we characterized O -glycosylation of LDLR-related proteins and identified conserved O -glycosylation sites in the LA linker regions of VLDLR, LRP1, and LRP2 (Megalin) from both cell lines and rat organs. Using a panel of gene-edited isogenic cell line models, we demonstrate that GalNAc-T11-mediated LDLR and VLDLR O -glycosylation is not required for transport and cell-surface expression and stability of these receptors but markedly enhances LDL and VLDL binding and uptake. Direct ELISA-based binding assays with truncated LDLR constructs revealed that O -glycosylation increased affinity for LDL by ∼5-fold. The molecular basis for this observation is currently unknown, but these findings open up new avenues for exploring the roles of LDLR-related proteins in disease. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Cancer-related fatigue and physical activity among premenopausal cervical and endometrial cancer survivors in Japan.

    Science.gov (United States)

    Obama, Kyoko; Maru, Mitsue; Maeda, Rumi; Kubota, Toshiro

    2015-09-30

    To examine the relationship between cancer-related fatigue (CRF) and physical activity in daily living in premenopausal disease-free cervical and endometrial cancer survivors. A physical activity monitor was used to collect objective data on daily physical activity. CRF and related variables were measured using self-report scales in a cross-sectional manner. The average age was 44.9 years among 64 women. The higher CRF group comprised 22 women (34%), 10% of whom had severe fatigue. The participants had higher physical activity levels compared with the findings in previous studies, and reported an average of 40 min/day of moderate to vigorous activity. Moderate to vigorous levels of physical activity were derived from essential social activities rather than leisure time exercise. There were no significant differences in physical activity levels between the lower and higher CRF groups. Our study results suggested that the higher level of physical activity in daily living itself had no relationship with decreasing CRF among premenopausal cervical and endometrial cancer survivors. It would be better to focus on cognitive and psychological factors before introducing physical activity programs and be careful of the characteristics of the participants' physical activity among this population in daily basis.

  1. Estimating the temporal distribution of exposure-related cancers

    International Nuclear Information System (INIS)

    Carter, R.L.; Sposto, R.; Preston, D.L.

    1993-09-01

    The temporal distribution of exposure-related cancers is relevant to the study of carcinogenic mechanisms. Statistical methods for extracting pertinent information from time-to-tumor data, however, are not well developed. Separation of incidence from 'latency' and the contamination of background cases are two problems. In this paper, we present methods for estimating both the conditional distribution given exposure-related cancers observed during the study period and the unconditional distribution. The methods adjust for confounding influences of background cases and the relationship between time to tumor and incidence. Two alternative methods are proposed. The first is based on a structured, theoretically derived model and produces direct inferences concerning the distribution of interest but often requires more-specialized software. The second relies on conventional modeling of incidence and is implemented through readily available, easily used computer software. Inferences concerning the effects of radiation dose and other covariates, however, are not always obtainable directly. We present three examples to illustrate the use of these two methods and suggest criteria for choosing between them. The first approach was used, with a log-logistic specification of the distribution of interest, to analyze times to bone sarcoma among a group of German patients injected with 224 Ra. Similarly, a log-logistic specification was used in the analysis of time to chronic myelogenous leukemias among male atomic-bomb survivors. We used the alternative approach, involving conventional modeling, to estimate the conditional distribution of exposure-related acute myelogenous leukemias among male atomic-bomb survivors, given occurrence between 1 October 1950 and 31 December 1985. All analyses were performed using Poisson regression methods for analyzing grouped survival data. (J.P.N.)

  2. Measuring the societal burden of cancer: the cost of lost productivity due to premature cancer-related mortality in Europe.

    Science.gov (United States)

    Hanly, Paul; Soerjomataram, Isabelle; Sharp, Linda

    2015-02-15

    Every cancer-related death in someone of working age represents an economic loss to society. To inform priorities for cancer control, we estimated costs of lost productivity due to premature cancer-related mortality across Europe, for all cancers and by site, gender, region and country. Cancer deaths in 2008 were obtained from GLOBOCAN for 30 European countries across four regions. Costs were valued using the human capital approach. Years of productive life lost (YPLL) were computed by multiplying deaths between 15 and 64 years by working-life expectancy, then by country-, age- and gender-specific annual wages, corrected for workforce participation and unemployment. Lost productivity costs due to premature cancer-related mortality in Europe in 2008 were €75 billion. Male costs (€49 billion) were almost twice female costs (€26 billion). The most costly sites were lung (€17 billion; 23% of total costs), breast (€7 billion; 9%) and colorectum (€6 billion; 8%). Stomach cancer (in Southern and Central-Eastern Europe) and pancreatic cancer (in Northern and Western Europe) were also among the most costly sites. The average lost productivity cost per cancer death was €219,241. Melanoma had the highest cost per death (€312,798), followed by Hodgkin disease (€306,628) and brain and CNS cancer (€288,850). Premature mortality costs were 0.58% of 2008 European gross domestic product, highest in Central-Eastern Europe (0.81%) and lowest in Northern Europe (0.51%). Premature cancer-related mortality costs in Europe are significant. These results provide a novel perspective on the societal cancer burden and may be used to inform priority setting for cancer control. © 2014 UICC.

  3. PREVALENCE, MECHANISMS, AND MANAGEMENT OF CANCER-RELATED COGNITIVE IMPAIRMENT

    Science.gov (United States)

    Janelsins, Michelle C.; Kesler, Shelli R.; Ahles, Tim A.; Morrow, Gary R.

    2014-01-01

    This review summarizes the current literature on cancer-related cognitive impairment (CRCI) with a focus on prevalence, mechanisms, and possible interventions for CRCI in those who receive adjuvant chemotherapy for non-central nervous system tumors and is primarily focused on breast cancer. CRCI is characterized as deficits in areas of cognition including memory, attention, concentration, and executive function. Development of CRCI can impair quality of life and impact treatment decisions. CRCI is highly prevalent; these problems can be detected in up to 30% of patients prior to chemotherapy; up to 75% of patients report some form of CRCI during treatment, and CRCI is still present in up to 35% of patients many years following completion of treatment. While the trajectory of CRCI is becoming better understood, the mechanisms underlying the development of CRCI are still obscure; however, host characteristics, immune dysfunction, neural toxicity, and genetics may play key roles in the development and trajectory of CRCI. Intervention research is limited, though strategies to maintain function are being studied with promising preliminary findings. This review highlights key research being conducted in these areas, both in patient populations and in animals, which will ultimately result in better understanding and effective treatments for CRCI. PMID:24716504

  4. Trends in human papillomavirus-related oropharyngeal cancer in Israel.

    Science.gov (United States)

    Amit, Moran; Ilana, Kaplan; Avraham, Sharon Pelles; Binenbaum, Yoav; Bachar, Gideon; Billan, Salem; Zaarura, Suliman; Czerninski, Rakefet; Bar-Tov, Matan; Maly, Alexander; Akrish, Sharon; Gil, Ziv

    2016-04-01

    The role of human papillomavirus (HPV) infection in oropharyngeal cancer (SCC) is well established. The annual incidence of oropharyngeal SCC in Israel is considerably lower than that in the United States. The purpose of this study was to assess the rate of HPV-related oropharyngeal SCC in Israel. The cohort included patients with oropharyngeal SCC who were treated during 1999 to 2011 in Israel. HPV typing was carried out using reverse hybridization and immunohistochemistry. Of the 74 patients analyzed, 25 (33.7%) had detectable HPV DNA. Patients in the HPV-positive group tended to be younger, with a higher rate of nodal metastases, and no history of smoking (p Israel as approximately 3-fold lower than in Western countries. Low exposure to HPV-16, a lower rate of transformation, to cancer or protective genetic factors may contribute to the lower rate of oropharyngeal SCC in Israel. © 2015 Wiley Periodicals, Inc. Head Neck 38: E274-E278, 2016. © 2015 Wiley Periodicals, Inc.

  5. [Relation between physical activity, weight balance and breast cancer].

    Science.gov (United States)

    Maître, Carole

    2013-05-01

    Many epidemiologic studies, with a good methodology, support the evidence of the positive role of regular physical activity on primary and tertiary prevention of breast cancer on the risk of recurrence and mortality. This relation depends on the level of total energy expenditure by week, which helps balance weight on lifetime, an essential part of benefit. The beneficial effects of physical activity are linked to many interrelated additional mechanisms: in a short-term, contraction of skeletal muscles involves aerobic metabolism which utilizes glucose and amino acids like glutamine, improves insulin sensitivity and lowers plasma insulin; in a long-term, physical activity produces favorable changes in body composition, decreasing body fat and increasing lean mass. That is a key point to reduce the intake of energy substrates stimulating carcinogenesis, to improve insulin sensitivity, to change the ratio of leptin and adiponectin, to enhance cellular immunity and to block cellular pathways of cell proliferation and angiogenesis. Maintaining a healthy weight through regular physical activity well balanced with energy intake is it a goal for prevention of breast cancer. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  6. Cigarette smoking and radiation exposure in relation to cancer mortality, Hiroshima and Nagasaki

    International Nuclear Information System (INIS)

    Prentice, R.L.; Yoshimoto, Yasuhiko; Mason, M.W.

    1983-05-01

    Cancer mortality among 40,498 Hiroshima and Nagasaki residents was examined in relation to cigarette smoking habits and estimated atomic bomb radiation exposure. Relative risk models that are either multiplicative or additive in the two exposures (smoking radiation) were emphasized. Most analyses were directed toward all nonhematologic cancer, stomach cancer, lung cancer, or digestive cancer other than stomach, for which there were, respectively, 1,725, 658, 281, and 338 deaths in the follow-up period of this study. Persons heavily exposed to both cigarette smoke and radiation were found to have significantly lower cancer mortality than multiplcative relative risk models would suggest for all nonhematologic cancer, stomach cancer, and digestive cancer other than stomach. Surprisingly, the relative risk function appeared not only to be submultiplicative for these cancer sites, but to be subadditive as well. The lung cancer relative risk function could not be distinguished from either a multiplicative or an additive form. The number of deaths was sufficient to permit some more detailed study of all nonhematologic cancer mortality: Relative risk functions appeared to be consistent between males and females though a paucity of heavy smoking females limits the precision of this comparison. (author)

  7. The relation between endometriosis and ovarian cancer - a review

    DEFF Research Database (Denmark)

    Nyhøj Heidemann, Lene; Hartwell, Dorthe; Heidemann, Christian Hamilton

    2014-01-01

    Endometriosis is known to harbor characteristics substantiating that it is a possible precursor of ovarian cancer.......Endometriosis is known to harbor characteristics substantiating that it is a possible precursor of ovarian cancer....

  8. Drug Reduces Cancer Treatment-Related Joint Pain

    Science.gov (United States)

    A Cancer Currents blog post about a clinical trial demonstrating that duloxetine (Cymbalta®) may reduce joint pain caused by aromatase inhibitors in women being treated for early-stage breast cancer.

  9. Chemical structure, biosynthesis and synthesis of free and glycosylated pyridinolines formed by cross-link of bone and synovium collagen.

    Science.gov (United States)

    Anastasia, Luigi; Rota, Paola; Anastasia, Mario; Allevi, Pietro

    2013-09-21

    This review focuses on the chemical structure, biosynthesis and synthesis of free and glycosylated pyridinolines (Pyds), fluorescent collagen cross-links, with a pyridinium salt structure. Pyds derive from the degradation of bone collagen and have attracted attention for their use as biochemical markers of bone resorption and to assess fracture risk prediction in persons suffering from osteoporosis, bone cancer and other bone or collagen diseases. We consider and critically discuss all reported syntheses of free and glycosylated Pyds evidencing an unrevised chemistry, original and of general utility, analysis of which allows us to also support a previously suggested non-enzymatic formation of Pyds in collagen better rationalizing and justifying the chemical events.

  10. Health-related quality of life in early breast cancer.

    Science.gov (United States)

    Groenvold, Mogens

    2010-09-01

    The treatment of primary breast cancer usually consists of surgery often followed by adjuvant therapy (radiotherapy, chemotherapy, hormonal treatment, etc.) to reduce the risk of recurrence. The cancer diagnosis and the treatments may have significant impact on the patients' quality of life. This thesis deals with scientific aspects and clinical results of a study aimed at assessing the impact of breast cancer (and its treatment) on the patients' quality of life. Studies such as this assessing the problems and symptoms experienced by the patients are often referred to as health-related quality of life (HRQL) research. HRQL research deals with subjective experiences and raises challenging, scientific questions. Therefore, much attention was directed towards methodological issues in this clinically motivated project. The study was a prospective, longitudinal, questionnaire-based investigation of women with newly diagnosed breast cancer registered in the Danish Breast Cancer Co-operative Group's DBCG 89 Program. The patients were sub-divided into low-risk and high-risk patients. High-risk patients were offered randomisation in one of three randomised adjuvant therapy trials involving chemotherapy, ovarian ablation, and endocrine therapy. After a literature study and interviews with breast cancer patients, a questionnaire was composed that included two widely used standard questionnaires (EORTC QLQ-C30 and Hospital Anxiety and Depression (HAD) Scale) and a DBCG 89 Questionnaire developed for this study. A total of 1,898 eligible patients were invited by post to participate in the study involving six assessments over a 2-year period, and 1,713 patients (90%) completed the first questionnaire. Furthermore, a questionnaire was sent to 872 women selected at random from the general population; 608 (70%) responded. The multi-item scales of the two standard questionnaires were analysed for so-called differential item functioning (DIF) in order to investigate whether the

  11. Doxorubicin attached to HPMA copolymer via amide bond modifies the glycosylation pattern of EL4 cells.

    Science.gov (United States)

    Kovar, Lubomir; Etrych, Tomas; Kabesova, Martina; Subr, Vladimir; Vetvicka, David; Hovorka, Ondrej; Strohalm, Jiri; Sklenar, Jan; Chytil, Petr; Ulbrich, Karel; Rihova, Blanka

    2010-08-01

    To avoid the side effects of the anti-cancer drug doxorubicin (Dox), we conjugated this drug to a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone. Dox was conjugated via an amide bond (Dox-HPMA(AM), PK1) or a hydrazone pH-sensitive bond (Dox-HPMA(HYD)). In contrast to Dox and Dox-HPMA(HYD), Dox-HPMA(AM) accumulates within the cell's intracellular membranes, including those of the Golgi complex and endoplasmic reticulum, both involved in protein glycosylation. Flow cytometry was used to determine lectin binding and cell death, immunoblot to characterize the presence of CD7, CD43, CD44, and CD45, and high-performance anion exchange chromatography with pulsed amperometric detector analysis for characterization of plasma membrane saccharide composition. Incubation of EL4 cells with Dox-HPMA(AM) conjugate, in contrast to Dox or Dox-HPMA(HYD), increased the amounts of membrane surface-associated glycoproteins, as well as saccharide moieties recognized by peanut agglutinin, Erythrina cristagalli, or galectin-1 lectins. Only Dox-HPMA(AM) increased expression of the highly glycosylated membrane glycoprotein CD43, while expression of others (CD7, CD44, and CD45) was unaffected. The binding sites for galectin-1 are present on CD43 molecule. Furthermore, we present that EL4 treated with Dox-HPMA(AM) possesses increased sensitivity to galectin-1-induced apoptosis. In this study, we demonstrate that Dox-HPMA(AM) treatment changes glycosylation of the EL4 T cell lymphoma surface and sensitizes the cells to galectin-1-induced apoptosis.

  12. HCV-related liver cancer in people with haemophilia

    NARCIS (Netherlands)

    Meijer, K.; Haagsma, E. B.

    . The topic of this monograph is liver cancer associated with chronic HCV infection. We start with some background information on chronic HCV infection and its long-term sequelae, one of which is liver cancer. The rest of the article is concerned with liver cancer or hepatocellular carcinoma (HCC).

  13. Surgical inpatient cancer-related mortality in a Nigerian tertiary ...

    African Journals Online (AJOL)

    Background: Cancer is a distressing condition that imposes so much physical, psychological and economic burden on the patients. Knowledge of the mortality pattern of cancers in any institution will enable the development of tailored preventive and therapeutic strategies. Aim: To present the cancer mortality patterns of ...

  14. Relative risk models of lung cancer in uranium miners

    Energy Technology Data Exchange (ETDEWEB)

    Tomasek, L [National Radiation Protection Institute, Prague (Czech Republic); Placek, V [Inst. for Expertises and Emergencies, Pribram-Kamenna (Czech Republic)

    1996-12-31

    The study population of the S cohort (studies of underground miners of uranium and other substances as the source of information on long term effects of exposure to radon and its progeny) involve uranium miners, that started underground work at the Jachymov and Horni Slavkov mines in the period 1978-1959, and had worked at least for four years. A total 4320 men satisfied these criteria. During the decade up to 1990, follow-up of the cohort mainly relied on the national population registry. In order to improve the follow-u, a series of additional checks were conducted: in the files of the Czech and Slovak Pensions Offices, by local enquires, and by direct correspondence. These additional efforts resulted in an increase of more than 10% in the numbers of known men to have died or emigrated. An exceptional feature of the S study is the large number of measurements of radon concentrations made in each mine-shaft (mean number per year and shaft was 223 in the period 1949-1960). Each man`s annual exposures to radon progeny in terms of working levels were estimated combining measurement data with men`s employment details. The excess relative risk models were used in the form RR = c(1 + ERR(w,x)), where ERR is excess relative risk, w and x denote exposure history and modifying variable, and c is an intercept term that allows the mortality rate for `unexposed` cohort to differ from that in the general population. The increased mortality (O/E=1.58; where O is observed and E is expected cases among collected death cases in the cohort) in the cohort, generally, somewhat lower ratios than one reflect the non-industrial character of the region, with the exception of lung cancer in man. The differences in the O/E ratios for lung cancer among the separate communities indicate that even in the situation of generally lower mortality, the dependence of lung cancer mortality on radon exposure cannot be excluded. 3 tabs., 6 refs.

  15. Blood pressure reduction due to hemoglobin glycosylation in type 2 diabetic patients

    Directory of Open Access Journals (Sweden)

    Pedro Cabrales

    2008-08-01

    Full Text Available Pedro Cabrales1, Miguel A Salazar Vázquez2,3, Beatriz Y Salazar Vázquez3,4, Martha Rodríguez-Morán5, Marcos Intaglietta4, Fernando Guerrero-Romero51La Jolla Bioengineering Institute, La Jolla, California, USA; 2Hospital Regional No. 1, of the Mexican Social Security Institute, Victoria de Durango, Dgo. Mexico; 3Faculty of Medicine and Dept. of Physical Chemistry, Universidad Juárez del Estado de Durango, Victoria de Durango, Dgo. Mexico; 4Department of Bioengineering, University of California, San Diego, La Jolla, California, USA; 5Biomedical Research Unit, of the Mexican Social Security Institute, Victoria de Durango, Dgo. MexicoObjective: To test the hypothesis that glycosylation of hemoglobin constitutes a risk factor for hypertension.Methods: A total of 129 relative uniform diabetic subjects (86 women and 42 men were enrolled in a cross-sectional study. Exclusion criteria included alcohol consumption, smoking, ischemic heart disease, stroke, neoplasia, renal, hepatic, and chronic inflammatory disease. Systolic and diastolic pressures were recorded in subsequent days and mean arterial blood pressure (MAP was determined. Hemoglobin glycosylation was measured by determining the percentage glycosylated hemoglobin (HbA1c by means of the automated microparticle enzyme immunoassay test.Results: MAP was found to be independent of the concentration of HbA1c; however, correcting MAP for the variability in hematocrit, to evidence the level of vasoconstriction (or vasodilatation showed that MAP is negatively correlated with the concentration of HbA1c (p for trend <0.05, when patients treated for hypertension are excluded from the analysis. Patients treated for hypertension showed the opposite trend with increasing MAP as HbA1c increased (p for the difference in trends <0.05.Conclusions: Glycosylation per se appears to lead to blood pressure reduction in type 2 diabetic patients untreated for hypertension. Treatment for hypertension may be

  16. Predictive values of symptoms in relation to cancer diagnosis

    DEFF Research Database (Denmark)

    Krasnik, Ivan; Andersen, John Sahl

    a manual describing the symptoms that should engender reasonable suspicion of malignancy (“alarm symptoms”) to the general practitioner. Objectives: To investigate the evidence in the literature of the predictive value (PPV) placed on the”alarm symptoms” for colon cancer, breast cancer, prostate cancer...... years (6,6%-21,2%), but much lower in younger age groups. ”Change in bowel habits” and ”Significant general symptoms” are more uncertain (3,5%-8,5%). Breast cancer: ”Palpable suspect tumor” is well supported (8,1%-24%). The predictive value of ”Pitting of the skin”, ”Papil-areola eczema......Background/significance: Poorer prognosis for cancer patients in Denmark than in comparable countries has been shown and contributed to the introduction of accelerated diagnostic trajectories for patients suspicious for cancer in 2008. For all types of cancers the National Board of Health developed...

  17. Enhancing Accuracy in Molecular Weight Determination of Highly Heterogeneously Glycosylated Proteins by Native Tandem Mass Spectrometry

    NARCIS (Netherlands)

    Wang, Guanbo; de Jong, Rob N; van den Bremer, Ewald T J; Parren, Paul W H I; Heck, Albert J R

    2017-01-01

    The determination of molecular weights (MWs) of heavily glycosylated proteins is seriously hampered by the physicochemical characteristics and heterogeneity of the attached carbohydrates. Glycosylation impacts protein migration during sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis

  18. The 'sweet' spot of cellular pluripotency: protein glycosylation in human pluripotent stem cells and its applications in regenerative medicine.

    Science.gov (United States)

    Wang, Yu-Chieh; Lin, Victor; Loring, Jeanne F; Peterson, Suzanne E

    2015-05-01

    Human pluripotent stem cells (hPSCs) promise for the future of regenerative medicine. The structural and biochemical diversity associated with glycans makes them a unique type of macromolecule modification that is involved in the regulation of a vast array of biochemical events and cellular activities including pluripotency in hPSCs. The primary focus of this review article is to highlight recent advances in stem cell research from a glycobiological perspective. We also discuss how our understanding of glycans and glycosylation may help overcome barriers hindering the clinical application of hPSC-derived cells. A literature survey using NCBI-PubMed and Google Scholar was performed in 2014. Regenerative medicine hopes to provide novel strategies to combat human disease and tissue injury that currently lack effective therapies. Although progress in this field is accelerating, many critical issues remain to be addressed in order for cell-based therapy to become a practical and safe treatment option. Emerging evidence suggests that protein glycosylation may significantly influence the regulation of cellular pluripotency, and that the exploitation of protein glycosylation in hPSCs and their differentiated derivatives may lead to transformative and translational discoveries for regenerative medicine. In addition, hPSCs represent a novel research platform for investigating glycosylation-related disease.

  19. Benefits of marriage on relative and conditional relative cancer survival differ between males and females in the USA.

    Science.gov (United States)

    Merrill, Ray M; Johnson, Erin

    2017-10-01

    The purpose of the paper is to assess the influence of marital status on conditional relative survival of cancer according to sex. Analyses involved 779,978 males and 1,032,868 females diagnosed with 1 of 13 cancer types between 2000 and 2008, and followed through 2013. Data are from the Surveillance, Epidemiology, and End Results (SEER) Program. Regression models were adjusted for age, sex, race, and tumor stage. Five-year relative survival conditional on years already survived is higher among married patients with less lethal cancers (oral cavity and pharynx, colon and rectum, breast, urinary bladder, kidney and renal pelvis, melanoma of the skin, thyroid, lymphoma). For more lethal cancers, married patients have similar (liver, lung and bronchus, pancreas, leukemia) or poorer (brain and other nervous system) cancer survival. Separated/divorced or widowed patients have the lowest conditional relative survival rates. For most cancers, 5-year cancer relative survival rates conditional on time already survived through 5 years approach 70 to 90% of that for the general population. The beneficial effect of marriage on survival decreases with years already survived. Superior conditional relative survival rates in females decrease with time already survived and are less pronounced in married patients. Five-year relative survival rates improve with time already survived. The benefits of marriage on conditional relative survival are greater for less lethal cancers. Greater 5-year conditional relative survival rates in females narrow with time already survived and are less pronounced in married patients. Conditional relative survival rates of cancer can lead to more informed decisions and understanding regarding treatment and prognosis.

  20. cancer metastasis and anti-cancer vaccines

    Indian Academy of Sciences (India)

    Glycosylation changes are universal hallmarks of malignant transformation and tumour progression in human cancer, which take place on the whole cells or some specific molecules. Accordingly, those changes make them prominent candidates for cancer biomarkers in the meantime. This review mainly focuses on the ...

  1. Health-related quality of life of African-American female breast cancer survivors, survivors of other cancers, and those without cancer.

    Science.gov (United States)

    Claridy, Mechelle D; Ansa, Benjamin; Damus, Francesca; Alema-Mensah, Ernest; Smith, Selina A

    2018-04-27

    The purpose of this study was to compare differences in health-related quality of life (HRQOL) between African-American female breast cancer survivors, African-American female survivors of other cancers, and African-American women with no history of cancer. Using data from the 2010 National Health Interview Survey (NHIS), the HRQOL of African-American women aged 35 years or older was compared by cancer status. Physical and mental health items from the Patient-Reported Outcomes Measurement Information System (PROMIS) global health scale were used to assess differences in HRQOL. For summary physical and mental health measures, no significant differences were found between breast cancer survivors and women with no history of cancer; survivors of other cancers reported poorer physical and mental health than did women with no history of cancer. Similar differences were found at the item level. When we examined the two African-American female cancer survivor groups, we found that cancer survivors whose cancer was being treated reported substantially poorer physical health and mental health than did those whose cancer was not being treated. Survivors who had private insurance and were cancer free reported better physical and mental health than did those who did not have private insurance and those who were not cancer free. Breast cancer survivors reported slightly better physical and mental health than did survivors of other cancers. Our findings highlight the need for public health agencies to adopt practices to improve the mental and physical health of African-American female survivors of cancer.

  2. Micropinocytic ingestion of glycosylated albumin by isolated microvessels: possible role in pathogenesis of diabetic microangiopathy.

    OpenAIRE

    Williams, S K; Devenny, J J; Bitensky, M W

    1981-01-01

    Microvessels isolated from rat epididymal fat exhibit differential vesicular ingestion rates for unmodified and non-enzymatically glycosylated rat albumin. While unmodified rat albumin is excluded from ingestion by endothelial micropinocytic vesicles, glycosylated albumin is avidly taken up by endocytosis. Interaction of albumin and glycosylated albumin with endothelium was studied with a double-label fluorescence assay of micropinocytosis. When glycosylated albumin was present at a concentra...

  3. Quality of Working Life of cancer survivors: associations with health- and work-related variables.

    Science.gov (United States)

    de Jong, Merel; Tamminga, Sietske J; Frings-Dresen, Monique H W; de Boer, Angela G E M

    2017-05-01

    This study aimed to (1) describe the Quality of Working Life (QWL) of cancer survivors and (2) explore associations between the QWL of cancer survivors and health- and work-related variables. Employed and self-employed cancer survivors were recruited through hospitals and patient organizations. They completed the Quality of Working Life Questionnaire for Cancer Survivors (QWLQ-CS) and health- and work-related variables in this cross-sectional study. The QWL scores of cancer survivors were described, and associations between QWL and health- and work-related variables were assessed. The QWLQ-CS was completed by 302 cancer survivors (28% male) with a mean age of 52 ± 8 years. They were diagnosed between 0 and 10 years ago with various types of cancer, such as breast cancers, gastrointestinal cancers, urological cancers, and haematological cancers. The QWL mean score of cancer survivors was 75 ± 12 (0-100). Cancer survivors had statistically significant lower QWL scores when they had been treated with chemotherapy or when they reported co-morbidity (p ≤ 0.05). Cancer survivors without managerial positions, with low incomes or physically demanding work, and who worked a proportion of their contract hours had statistically significantly lower QWL scores (p ≤ 0.05). This study described the QWL of cancer survivors and associations between QWL and health- and work-related variables. Based on these variables, it is possible to indicate groups of cancer survivors who need more attention and support regarding QWL and work continuation.

  4. A computerized Stroop task to assess cancer-related cognitive biases.

    Science.gov (United States)

    DiBonaventura, Marco DaCosta; Erblich, Joel; Sloan, Richard P; Bovbjerg, Dana H

    2010-01-01

    Biases in processing information related to sources of stress have widely been demonstrated with the use of Stroop emotional color word tasks. One study reported such biases among women with histories of breast cancer in a first-degree relative (FH+) who were given a Stroop cancer word task. This study aimed to replicate and extend these findings with a computerized version of the task. Response latencies and errors were recorded during administration of the task to FH+ and FH- women. A cancer list and 5 comparison lists were administered. Results indicated that FH+ women exhibited longer response latencies for cancer words than did FH- women (p Stroop cancer word task.

  5. N-Glycosylation of Carnosinase Influences Protein Secretion and Enzyme Activity Implications for Hyperglycemia

    NARCIS (Netherlands)

    Riedl, Eva; Koeppel, Hannes; Pfister, Frederick; Peters, Verena; Sauerhoefer, Sibylle; Sternik, Paula; Brinkkoetter, Paul; Zentgraf, Hanswalter; Navis, Gerjan; Henning, Robert H.; Van Den Born, Jacob; Bakker, Stephan J. L.; Janssen, Bart; van der Woude, Fokko J.; Yard, Benito A.

    OBJECTIVE-The (CTG)(n) polymorphism in the serum carnosinase (CN-1) gene affects CN-1 secretion Since CN-1 is heavily glycosylated and glycosylation might influence protein secretion as well, we tested the role of N-glycosylation for CN-1 secretion and enzyme activity. We also tested whether CN-1

  6. Effect of Cola acuminate on Blood Glucose and Glycosylated ...

    African Journals Online (AJOL)

    The levels of blood glucose and glycosylated haemoglobin (GHB) were studied in 42 Wistar rats divided into three groups; controls, group A and group B. Control rats consumed only feeds, group A consumed 0.04g of Cola acuminate, while group B consumed 0.08g of Cola acuminate mixed with their feeds daily for six ...

  7. Perinatal and early infantile symptoms in congenital disorders of glycosylation

    NARCIS (Netherlands)

    Funke, S.; Gardeitchik, T.; Kouwenberg, D.; Mohamed, M.; Wortmann, S.B.; Korsch, E.; Adamowicz, M.; Al-Gazali, L.; Wevers, R.A.; Horvath, A.; Lefeber, D.J.; Morava, E.

    2013-01-01

    Congenital disorders of glycosylation (CDG) are a rapidly growing family of inborn errors. Screening for CDG in suspected cases is usually performed in the first year of life by serum transferrin isoelectric focusing or mass spectrometry. Based on the transferrin analysis patients can be

  8. SnapShot: O-Glycosylation Pathways across Kingdoms

    DEFF Research Database (Denmark)

    Joshi, Hiren J.; Narimatsu, Yoshiki; Schjoldager, Katrine T.

    2018-01-01

    O-glycosylation is one of the most abundant and diverse types of post-translational modifications of proteins. O-glycans modulate the structure, stability, and function of proteins and serve generalized as well as highly specific roles in most biological processes. This ShapShot presents types of......-glycans found in different organisms and their principle biosynthetic pathways...

  9. Chapter Three -- Glycosylation of Cellulases: Engineering Better Enzymes for Biofuels

    Energy Technology Data Exchange (ETDEWEB)

    Greene, Eric R. [Univ. of Colorado, Boulder, CO (United States). Dept. of Chemistry and Biochemistry and BioFrontiers Inst.; Himmel, Michael E. [National Renewable Energy Lab. (NREL), Golden, CO (United States). Biosciences Center; Beckham, Gregg T. [National Renewable Energy Lab. (NREL), Golden, CO (United States). National Bioenergy Center; Tan, Zhongping [Univ. of Colorado, Boulder, CO (United States). Dept. of Chemistry and Biochemistry and BioFrontiers Inst.

    2015-10-24

    Methods for the manipulation of glycan structures have been recently reported that employ genetic tuning of glycan-active enzymes expressed from homogeneous and heterologous fungal hosts. Taken together, these studies have enabled new strategies for the exploitation of protein glycosylation for the production of enhanced cellulases for biofuel production.

  10. Predictive glycoengineering of biosimilars using a Markov chain glycosylation model

    DEFF Research Database (Denmark)

    Spahn, Philipp N.; Hansen, Anders Holmgaard; Kol, Stefan

    2017-01-01

    Biosimilar drugs must closely resemble the pharmacological attributes of innovator products to ensure safetyand efficacy to obtain regulatory approval. Glycosylation is one critical quality attribute that must be matched, but it is inherently difficult to control due to the complexity of its...

  11. Glycosylation patterns of kidney proteins differ in rat diabetic nephropathy.

    Science.gov (United States)

    Ravidà, Alessandra; Musante, Luca; Kreivi, Marjut; Miinalainen, Ilkka; Byrne, Barry; Saraswat, Mayank; Henry, Michael; Meleady, Paula; Clynes, Martin; Holthofer, Harry

    2015-05-01

    Diabetic nephropathy often progresses to end-stage kidney disease and, ultimately, to renal replacement therapy. Hyperglycemia per se is expected to have a direct impact on the biosynthesis of N- and O-linked glycoproteins. This study aims to establish the link between protein glycosylation and progression of experimental diabetic kidney disease using orthogonal methods. Kidneys of streptozotocin-diabetic and control rats were harvested at three different time points post streptozotocin injection. A panel of 12 plant lectins was used in the screening of lectin blots. The lectins UEAI, PHA-E, GSI, PNA, and RCA identified remarkable disease-associated differences in glycoprotein expression. Lectin affinity chromatography followed by mass spectrometric analyses led to the identification of several glycoproteins involved in salt-handling, angiogenesis, and extracellular matrix degradation. Our data confirm a substantial link between glycosylation signature and diabetes progression. Furthermore, as suggested by our findings on dipeptidyl peptidase-IV, altered protein glycosylation may reflect changes in biochemical properties such as enzymatic activity. Thus, our study demonstrates the unexplored potential of protein glycosylation analysis in the discovery of molecules linked to diabetic kidney disease.

  12. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Glycosylated hemoglobin assay. 864.7470 Section 864.7470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7470...

  13. Deciphering a pathway of Halobacterium salinarum N-glycosylation

    Science.gov (United States)

    Kandiba, Lina; Eichler, Jerry

    2015-01-01

    Genomic analysis points to N-glycosylation as being a common posttranslational modification in Archaea. To date, however, pathways of archaeal N-glycosylation have only been described for few species. With this in mind, the similarities of N-linked glycans decorating glycoproteins in the haloarchaea Haloferax volcanii and Halobacterium salinarum directed a series of bioinformatics, genetic, and biochemical experiments designed to describe that Hbt. salinarum pathway responsible for biogenesis of one of the two N-linked oligosaccharides described in this species. As in Hfx. volcanii, where agl (archaeal glycosylation) genes that encode proteins responsible for the assembly and attachment of a pentasaccharide to target protein Asn residues are clustered in the genome, Hbt. salinarum also contains a group of clustered homologous genes (VNG1048G-VNG1068G). Introduction of these Hbt. salinarum genes into Hfx. volcanii mutant strains deleted of the homologous sequence restored the lost activity. Moreover, transcription of the Hbt. salinarum genes in the native host, as well as in vitro biochemical confirmation of the predicted functions of several of the products of these genes provided further support for assignments made following bioinformatics and genetic experiments. Based on the results obtained in this study, the first description of an N-glycosylation pathway in Hbt. salinarum is offered. PMID:25461760

  14. Protocol for a systematic review of psychological interventions for cancer-related fatigue in post-treatment cancer survivors.

    Science.gov (United States)

    Corbett, Teresa; Devane, Declan; Walsh, Jane C; Groarke, AnnMarie; McGuire, Brian E

    2015-12-04

    Fatigue is a common symptom in cancer patients that can persist beyond the curative treatment phase. Some evidence has been reported for interventions for fatigue during active treatment. However, to date, there is no systematic review on psychological interventions for fatigue after the completion of curative treatment for cancer. This is a protocol for a systematic review that aims to evaluate the effectiveness of psychological interventions for cancer-related fatigue in post-treatment cancer survivors. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) database. We will search the Cochrane Central Register of Controlled Trials (CENTRAL; The Cochrane Library), PubMed, MEDLINE, EMBASE, CINAHL, PsycINFO, and relevant sources of grey literature. Randomised controlled trials (RCTs) which have evaluated psychological interventions in adult cancer patients after the completion of treatment, with fatigue as an outcome measure, will be included. Two review authors will independently extract data from the selected studies and assess the methodological quality using the Cochrane Collaboration Risk of Bias Tool. Most existing evidence on cancer-related fatigue is from those in active cancer treatment. This systematic review and meta-analysis will build upon previous evaluations of psychological interventions in people during and after cancer treatment. With the growing need for stage-specific research in cancer, this review seeks to highlight a gap in current practice and to strengthen the evidence base of randomised controlled trials in the area. PROSPERO CRD42014015219.

  15. Chemotherapy- and cancer-related nausea and vomiting

    OpenAIRE

    Warr, D.G.

    2008-01-01

    Approximately one half of cancer patients will experience nausea or vomiting during the course of their disease either because of the cancer itself or because of their treatment. Emesis attributable to cancer warrants a careful investigation to determine whether a treatable underlying cause is responsible. Interventions using dexamethasone and octreotide may reduce vomiting attributable to bowel obstruction. In the absence of a bowel obstruction or a correctable cause, the usual approach is a...

  16. Cancer-related symptoms predict psychological wellbeing among prostate cancer survivors: results from the PiCTure study.

    Science.gov (United States)

    Sharp, Linda; O'Leary, Eamonn; Kinnear, Heather; Gavin, Anna; Drummond, Frances J

    2016-03-01

    Prostate cancer treatments are associated with a range of symptoms and physical side-effects. Cancer can also adversely impact on psychological wellbeing. Because many prostate cancer-related symptoms and side-effects are potentially modifiable, we investigated associations between symptoms and psychological wellbeing among prostate cancer survivors. Postal questionnaires were distributed to men diagnosed with prostate cancer 2-18 years previously identified through cancer registries. General and prostate cancer-specific symptoms were assessed using the EORTC QLQ-C30 and QLQ-PR25, with higher symptom scores indicating more/worse symptomatology. Psychological wellbeing was assessed by the DASS-21. Associations between symptoms and each outcome were investigated using multivariate logistic regression, controlling for socio-demographic and clinical factors. A total 3348 men participated (response rate = 54%). Seventeen percent (95%CI 15.2%-17.9%), 16% (95%CI 15.1%-17.8%) and 11% (95%CI 9.5%-11.8%) of survivors scored in the range for depression, anxiety and distress on the DASS scales, respectively. In multivariate models, risk of depression on the DASS scale was significantly higher in men with higher urinary and androgen deprivation therapy (ADT)-related symptoms, and higher scores for fatigue, insomnia and financial difficulties. Risk of anxiety on the DASS scale was higher in men with higher scores for urinary, bowel and ADT-related symptoms and fatigue, dyspnoea and financial difficulties. Risk of distress on the DASS scale was positively associated with urinary, bowel and ADT-related symptoms, fatigue, insomnia and financial difficulties. Cancer-related symptoms significantly predict psychological wellbeing among prostate cancer survivors. Greater use of interventions and medications and to alleviate symptoms might improve psychological wellbeing of prostate cancer survivors. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Cancer immunotherapy and immune-related response assessment: The role of radiologists in the new arena of cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215 (United States); Tirumani, Sree H.; Ramaiya, Nikhil H. [Department of Radiology, Brigham and Women' s Hospital and Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215 (United States); Hodi, F. Stephen [Department of Medical Oncology and Department of Medicine, Dana-Farber Cancer Institute and Brigham and Women' s Hospital, 450 Brookline Ave., Boston, MA 02215 (United States)

    2015-07-15

    Highlights: • The successful clinical application of cancer immunotherapy has opened a new arena for the treatment of advanced cancers. • Cancer immunotherapy is associated with a variety of important radiographic features in the assessments of tumor response and immune-related adverse events. • The state-of-the art knowledge of immunotherapy and the related radiologic manifestations are essential for radiologists. - Abstract: The recent advances in the clinical application of anti-cancer immunotherapeutic agents have opened a new arena for the treatment of advanced cancers. Cancer immunotherapy is associated with a variety of important radiographic features in the assessments of tumor response and immune-related adverse events, which calls for radiologists’ awareness and in-depth knowledge on the topic. This article will provide the state-of-the art review and perspectives of cancer immunotherapy, including its molecular mechanisms, the strategies for immune-related response assessment on imaging and their pitfalls, and the emerging knowledge of radiologic manifestations of immune-related adverse events. The cutting edge clinical and radiologic investigations are presented to provide future directions.

  18. Cancer immunotherapy and immune-related response assessment: The role of radiologists in the new arena of cancer treatment

    International Nuclear Information System (INIS)

    Nishino, Mizuki; Tirumani, Sree H.; Ramaiya, Nikhil H.; Hodi, F. Stephen

    2015-01-01

    Highlights: • The successful clinical application of cancer immunotherapy has opened a new arena for the treatment of advanced cancers. • Cancer immunotherapy is associated with a variety of important radiographic features in the assessments of tumor response and immune-related adverse events. • The state-of-the art knowledge of immunotherapy and the related radiologic manifestations are essential for radiologists. - Abstract: The recent advances in the clinical application of anti-cancer immunotherapeutic agents have opened a new arena for the treatment of advanced cancers. Cancer immunotherapy is associated with a variety of important radiographic features in the assessments of tumor response and immune-related adverse events, which calls for radiologists’ awareness and in-depth knowledge on the topic. This article will provide the state-of-the art review and perspectives of cancer immunotherapy, including its molecular mechanisms, the strategies for immune-related response assessment on imaging and their pitfalls, and the emerging knowledge of radiologic manifestations of immune-related adverse events. The cutting edge clinical and radiologic investigations are presented to provide future directions

  19. Posttraumatic Stress and Attentional Bias towards Cancer-Related Stimuli in Parents of Children Recently Diagnosed with Cancer.

    Directory of Open Access Journals (Sweden)

    Martin Cernvall

    Full Text Available To investigate whether posttraumatic stress symptoms (PTSS are related to attentional bias towards cancer-related stimuli among parents of children recently diagnosed with cancer.Sixty-two parents completed questionnaires measuring PTSS, depression, and anxiety and the emotional Stroop task via the Internet. The emotional Stroop task included cancer-related words, cardiovascular disease-related words, and neutral words.Participants were split in two groups based on the median of PTSS: High-PTSS and Low-PTSS. There was a significant interaction between word-type and group and a planned contrast test of this interaction indicated that the High-PTSS group had longer response latencies on cancer-related words compared to the other word-type and group combinations.Findings suggest that PTSS are related to attentional bias towards cancer-related stimuli among parents of children recently diagnosed with cancer. Implications of this finding for the understanding of PTSS in this population, future research, and clinical practice are discussed.

  20. EDEM2 and OS-9 are required for ER-associated degradation of non-glycosylated sonic hedgehog.

    Directory of Open Access Journals (Sweden)

    Hsiang-Yun Tang

    Full Text Available Misfolded proteins of the endoplasmic reticulum (ER are eliminated by the ER-associated degradation (ERAD in eukaryotes. In S. cerevisiae, ER-resident lectins mediate substrate recognition through bipartite signals consisting of an unfolded local structure and the adjacent glycan. Trimming of the glycan is essential for the directional delivery of the substrates. Whether a similar recognition and delivery mechanism exists in mammalian cells is unknown. In this study, we systematically study the function and substrate specificity of known mammalian ER lectins, including EDEM1/2/3, OS-9 and XTP-3B using the recently identified ERAD substrate sonic hedgehog (SHH, a soluble protein carrying a single N-glycan, as well as its nonglycosylated mutant N278A. Efficient ERAD of N278A requires the core processing complex of HRD1, SEL1L and p97, similar to the glycosylated SHH. While EDEM2 was required for ERAD of both glycosylated and non-glycosylated SHHs, EDEM3 was only necessary for glycosylated SHH and EDEM1 was dispensable for both. Degradation of SHH and N278A also required OS-9, but not the related lectin XTP3-B. Robust interaction of both EDEM2 and OS-9 with a non-glycosylated SHH variant indicates that the misfolded polypeptide backbone, rather than a glycan signature, functions as the predominant signal for recognition for ERAD. Notably, SHH-N278A is the first nonglycosylated substrate to require EDEM2 for recognition and targeting for ERAD. EDEM2 also interacts with calnexin and SEL1L, suggesting a potential avenue by which misfolded glycoproteins may be shunted towards SEL1L and ERAD rather than being released into the secretory pathway. Thus, ER lectins participate in the recognition and delivery of misfolded ER substrates differently in mammals, with an underlying mechanism distinct from that of S. cerevisiae.

  1. Impact of O-glycosylation on the molecular and cellular adhesion properties of the Escherichia coli autotransporter protein Ag43.

    Science.gov (United States)

    Reidl, Sebastian; Lehmann, Annika; Schiller, Roswitha; Salam Khan, A; Dobrindt, Ulrich

    2009-08-01

    Antigen 43 (Ag43) represents an entire family of closely related autotransporter proteins in Escherichia coli and has been described to confer aggregation and fluffing of cells, to promote biofilm formation, uptake and survival in macrophages as well as long-term persistence of uropathogenic E. coli in the murine urinary tract. Furthermore, it has been reported that glycosylation of the Ag43 passenger domain (alpha(43)) stabilizes its conformation and increases adhesion to Hep-2 cells. We characterized the role of Ag43 as an adhesin and the impact of O-glycosylation on the function of Ag43. To analyze whether structural variations in the alpha(43) domain correlate with different functional properties, we cloned 5 different agn43 alleles from different E. coli subtypes and tested them for autoaggregation, biofilm formation, adhesion to different eukaryotic cell lines as well as to purified components of the extracellular matrix. These experiments were performed with nonglycosylated and O-glycosylated Ag43 variants. We show for the first time that Ag43 mediates bacterial adhesion in a cell line-specific manner and that structural variations of the alpha(43) domain correlate with increased adhesive properties to proteins of the extracellular matrix such as collagen and laminin. Whereas O-glycosylation of many alpha(43) domains led to impaired autoaggregation and a significantly reduced adhesion to eukaryotic cell lines, their interaction with collagen was significantly increased. These data demonstrate that O-glycosylation is not a prerequisite for Ag43 function and that the different traits mediated by Ag43, i.e., biofilm formation, autoaggregation, adhesion to eukaryotic cells and extracellular matrix proteins, rely on distinct mechanisms.

  2. N-glycosylated catalytic unit meets O-glycosylated propeptide: complex protein architecture in a fungal hexosaminidase

    Czech Academy of Sciences Publication Activity Database

    Plíhal, Ondřej; Sklenář, Jan; Kmoníčková, J.; Man, Petr; Pompach, Petr; Havlíček, Vladimír; Křen, Vladimír; Bezouška, Karel

    2004-01-01

    Roč. 32, č. 5 (2004), s. 764-765 ISSN 0300-5127 R&D Projects: GA ČR GA203/04/1045 Institutional research plan: CEZ:AV0Z5020903 Keywords : asperillus oryzoe * glycosyl hydrolase * preproprotein Subject RIV: EE - Microbiology, Virology Impact factor: 2.267, year: 2004

  3. State-Level Estimates of Cancer-Related Absenteeism Costs

    Science.gov (United States)

    Tangka, Florence K.; Trogdon, Justin G.; Nwaise, Isaac; Ekwueme, Donatus U.; Guy, Gery P.; Orenstein, Diane

    2016-01-01

    Background Cancer is one of the top five most costly diseases in the United States and leads to substantial work loss. Nevertheless, limited state-level estimates of cancer absenteeism costs have been published. Methods In analyses of data from the 2004–2008 Medical Expenditure Panel Survey, the 2004 National Nursing Home Survey, the U.S. Census Bureau for 2008, and the 2009 Current Population Survey, we used regression modeling to estimate annual state-level absenteeism costs attributable to cancer from 2004 to 2008. Results We estimated that the state-level median number of days of absenteeism per year among employed cancer patients was 6.1 days and that annual state-level cancer absenteeism costs ranged from $14.9 million to $915.9 million (median = $115.9 million) across states in 2010 dollars. Absenteeism costs are approximately 6.5% of the costs of premature cancer mortality. Conclusions The results from this study suggest that lost productivity attributable to cancer is a substantial cost to employees and employers and contributes to estimates of the overall impact of cancer in a state population. PMID:23969498

  4. MicroRNA related polymorphisms and breast cancer risk

    NARCIS (Netherlands)

    S. Khan (Sofia); D. Greco (Dario); K. Michailidou (Kyriaki); R.L. Milne (Roger); T.A. Muranen (Taru); T. Heikkinen (Tuomas); K. Aaltonen (Kirsimari); J. Dennis (Joe); M.K. Bolla (Manjeet); J. Liu (Jianjun); P. Hall (Per); A. Irwanto (Astrid); M.K. Humphreys (Manjeet); J. Li (Jingmei); K. Czene (Kamila); J. Chang-Claude (Jenny); R. Hein (Rebecca); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); O. Fletcher (Olivia); J. Peto (Julian); I. dos Santos Silva (Isabel); N. Johnson (Nichola); L.J. Gibson (Lorna); A. Aitken; J.L. Hopper (John); H. Tsimiklis (Helen); M. Bui (Minh); E. Makalic (Enes); D.F. Schmidt (Daniel); M.C. Southey (Melissa); C. Apicella (Carmel); J. Stone (Jennifer); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); M.A. Adank (Muriel); R.B. van der Luijt (Rob); A. Meindl (Alfons); R.K. Schmutzler (Rita); B. Müller-Myhsok (B.); P. Lichtner (Peter); C. Turnbull (Clare); N. Rahman (Nazneen); S.J. Chanock (Stephen); D. Hunter (David); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); M.K. Schmidt (Marjanka); A. Broeks (Annegien); L.J. van 't Veer (Laura); F.B.L. Hogervorst (Frans); P.A. Fasching (Peter); A. Schrauder (André); A.B. Ekici (Arif); M.W. Beckmann (Matthias); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); J. Benítez (Javier); P.M. Zamora (Pilar M.); J.I.A. Perez (Jose Ignacio Arias); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L.L. March (Loic Le); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); M. Shah (Mitul); R.N. Luben (Robert); J. Brown (Judith); F.J. Couch (Fergus); X. Wang (X.); C. Vachon (Celine); J.E. Olson (Janet); D. Lambrechts (Diether); M. Moisse (Matthieu); R. Paridaens (Robert); M.R. Christiaens (Marie Rose); P. Guénel (Pascal); T. Truong (Thérèse); P. Laurent-Puig (Pierre); C. Mulot (Claire); F. Marme (Frederick); B. Burwinkel (Barbara); A. Schneeweiss (Andreas); C. Sohn (Christof); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); I.L. Andrulis (Irene); J.A. Knight (Julia); S. Tchatchou (Srine); A.-M. Mulligan (Anna-Marie); T. Dörk (Thilo); N.V. Bogdanova (Natalia); N.N. Antonenkova (Natalia); H. Anton-Culver (Hoda); H. Darabi (Hatef); M. Eriksson (Mats); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); J. Lissowska (Jolanta); L.A. Brinton (Louise); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); V. Kristensen (Vessela); S. Slager (Susan); A.E. Tol (Ama E.); C.B. Ambrosone (Christine); D. Yannoukakos (Drakoulis); A. Lindblom (Annika); S. Margolin (Sara); P. Radice (Paolo); P. Peterlongo (Paolo); M. Barile (Monica); P. Mariani (Paolo); M.J. Hooning (Maartje); J.W.M. Martens (John); J.M. Collée (Margriet); A. Jager (Agnes); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); G.G. Giles (Graham); C.A. McLean (Catriona Ann); H. Brauch (Hiltrud); T. Brüning (Thomas); Y.-D. Ko (Yon-Dschun); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Jones (Michael); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); A. Mannermaa (Arto); U. Hamann (Ute); G. Chenevix-Trench (Georgia); C. Blomqvist (Carl); K. Aittomäki (Kristiina); D.F. Easton (Douglas); H. Nevanlinna (Heli)

    2014-01-01

    textabstractGenetic variations, such as single nucleotide polymorphisms (SNPs) in microRNAs (miRNA) or in the miRNA binding sites may affect the miRNA dependent gene expression regulation, which has been implicated in various cancers, including breast cancer, and may alter individual susceptibility

  5. Job related mortality risks of Hanford workers and their relation to cancer effects of measured doses of external radiation

    International Nuclear Information System (INIS)

    Kneale, G.W.; Mancuso, T.F.; Stewart, A.M.

    1984-01-01

    A continuation of the series by Mancuso, Stewart, and Kneale (MSK) on studies of cancer risks for radiation workers at Hanford is presented. It concentrates on the statistical problems posed by the need to estimate and control for job related mortality risks when there are several changes of occupation and no certainty about how different occupations are related to two socioeconomic factors which have strong health associations-namely, education and income. The final conclusion is that for tissues which are sensitive to cancer induced by radiation there is a risk of cancer for Hanford exposures whose dose response is curvilinear with long latency and increasing effect with increasing exposure age. (author)

  6. Healing environments in cancer treatment and care. Relations of space and practice in hematological cancer treatment.

    Science.gov (United States)

    Høybye, Mette Terp

    2013-02-01

    Given the growing attention to the importance of design in shaping healing hospital environments this study extends the understanding of healing environments, beyond causal links between environmental exposure and health outcome by elucidating how environments and practices interrelate. The study was conducted as an ethnographic fieldwork from March 2011 to September 2011 at the Department of Haematology at Odense University Hospital, Denmark, systematically using participant observation and interviews as research strategies. It included 20 patients, four of who were followed closely over an extended time period. Through thematic analysis five key concepts emerged about the social dynamics of hospital environments: practices of self; creating personal space; social recognition; negotiating space; and ambiguity of space and care. Through these concepts, the study demonstrates how the hospital environment is a flow of relations between space and practice that changes and challenges a structural idea of design and healing. Patients' sense of healing changes with the experience of progression in treatment and the capacity of the hospital space to incite an experience of homeliness and care. Furthermore, cancer patients continuously challenge the use and limits of space by individual objects and practices of privacy and home. Healing environments are complex relations between practices, space and care, where recognition of the individual patient's needs, values and experiences is key to developing the environment to support the patient quality of life. The present study holds implications for practice to inform design of future hospital environments for cancer treatment. The study points to the importance for being attentive to the need for flexible spaces in hospitals that recognize the dynamics of healing, by providing individualized care, relating to the particular and changing needs of patients supporting their potential and their challenged condition with the best

  7. Relative risks of radiation-associated cancer: comparison of second cancer in therapeutically irradiated populations with the Japanese atomic bomb survivors

    International Nuclear Information System (INIS)

    Little, M.P.; Muirhead, C.R.; Haylock, R.G.E.; Thomas, J.M.

    1999-01-01

    In this paper the radiation-associated relative risks of second primary cancer incidence in groups treated for first primary cancer by radiotherapy are compared with radiation-associated relative risk estimates in the Japanese atomic bomb survivor cancer incidence data. For four cancer sites, namely lung cancer, bone cancer, ovarian cancer and leukaemia, the relative risks in the comparable (age at exposure, time since exposure, sex matched) subsets of the Japanese data are significantly greater than those in the majority of second cancer studies. Even when the differences between the relative risks in the Japanese atomic bomb survivors and the medical series do not approach conventional levels of statistical significance, relative risks tend to be higher in the Japanese data than in the second cancer studies. At least for leukaemia, the discrepancy between the Japanese and second cancer risks can be largely explained by cell- sterilisation effects. There are few indications of modification of radiation-associated second cancer relative risk among those treated with adjuvant chemotherapy, nor are there strong indications of modification of radiation- associated relative risk by heritable genetic factors. If anything, there is evidence that second cancer relative excess risks are lower among those patients with cancer-prone disorders than among non-susceptible patients. However, the higher underlying cancer risk in some of these medically exposed populations should also be considered, in particular for those with cancer-prone conditions, so that the absolute excess risk is sometimes higher than in the Japanese data. (orig.)

  8. Discovery of the cancer stem cell related determinants of radioresistance

    International Nuclear Information System (INIS)

    Peitzsch, Claudia; Kurth, Ina; Kunz-Schughart, Leoni; Baumann, Michael; Dubrovska, Anna

    2013-01-01

    Tumors are known to be heterogeneous containing a dynamic mixture of phenotypically and functionally different tumor cells. The two concepts attempting to explain the origin of intratumor heterogeneity are the cancer stem cell hypothesis and the clonal evolution model. The stochastic model argues that tumors are biologically homogenous and all cancer cells within the tumor have equal ability to propagate the tumor growth depending on continuing mutations and selective pressure. By contrast, the stem cells model suggests that cancer heterogeneity is due to the hierarchy that originates from a small population of cancer stem cells (CSCs) which are biologically distinct from the bulk tumor and possesses self-renewal, tumorigenic and multilineage potential. Although these two hypotheses have been discussed for a long time as mutually exclusive explanations of tumor heterogeneity, they are easily reconciled serving as a driving force of cancer evolution and diversity. Recent discovery of the cancer cell plasticity and heterogeneity makes the CSC population a moving target that could be hard to track and eradicate. Understanding the signaling mechanisms regulating CSCs during the course of cancer treatment can be indispensable for the optimization of current treatment strategies

  9. Coping and emotional distress in relation to health-related quality of life in Slovene patients with cancer

    Directory of Open Access Journals (Sweden)

    Tanja Žagar

    2011-08-01

    Full Text Available Managing emotional distress triggers different coping strategies for coping with stress in cancer patients. Effective coping affects health – related quality of life and psychosocial adaptation. This study was performed to determine coping strategies, and their connectedness to emotional distress (anxiety and depression and health – related quality of life in cancer patients. Study was carried out on 70 cancer patients, in inpatient and outpatient setting. Depressive symptoms were measured with Beck Depression Inventory BDI-SH, anxiety with State Trait Anxiety Inventory STAI-1, coping strategies with Coping Response Inventory CRI and health – related quality of life with Quality of Life Questionnaire QOLQ- 30. A negative, statistically important relationship was found between active strategies, emotional distress and quality of life. Recognition of emotional distress and ways of coping in cancer patients are important for quality of health care.

  10. Risk for non-smoking-related cancer in atherosclerotic patients

    DEFF Research Database (Denmark)

    Dreyer, L; Olsen, J H

    1999-01-01

    Some studies have suggested that the pathogenesis of atherosclerosis and that of cancer have common features, and in addition to tobacco smoking, oxidative stress, diet, and sex hormones have been considered as common etiological factors. To investigate whether there is an association between...... in this group was calculated by linkage to the Danish Cancer Registry for the period 1977-1993. No consistent excesses over the expected figures were seen for cancer at any site unrelated to tobacco smoking in either the total cohort or in subgroups. Specifically, we found no association at the individual level...

  11. Patterns of glycemic control using glycosylated hemoglobin in diabetics

    Directory of Open Access Journals (Sweden)

    Arunpreet Singh Kahlon

    2011-01-01

    Full Text Available Aim : Till now estimation of blood glucose is the highly effective method for diagnosing diabetes mellitus but it provides a short-term picture of control. More evidence is required to prove that plasma glucose and glycosylated hemoglobin levels together gives a better estimate of glycemic control and compliance with treatment. Indian diabetes risk score (IDRS is a simplified screening tool for identifying undiagnosed diabetic subjects, requires minimum time, and effort and can help to considerably reduce the costs of screening. Objective : To study patterns of glycemic control using glycosylated hemoglobin in diabetic patients. To find out correlation between levels of plasma glucose and glycosylated hemoglobin in diabetics and to calculate IDRS of the study population. Materials and Methods : A cross sectional study was conducted among 300 known diabetic patients attending outpatient department of a rural medical college in Haryana, India. Following standard procedures and protocols FPG and glycosylated hemoglobin were measured to find out a pattern of glycemic control in them after taking their written and informed consent. A correlation between the levels of glycosylated hemoglobin and fasting blood glucose was also calculated. These patients were made to fill a performa and their demographic and clinical risk factors were noted and based on this, their IDRS was calculated. This was done to validate the IDRS in Indian rural population. Results : Fifty-two percent of the population had fasting plasma glucose level between 125-150 mg/dl, 21% had this level between 151-175 mg/dl. Thirteen percent of the study subjects had HbA1C between 6.5-7.5, more than half (57.3% had this value between 7.5-8.5, 12% and 18% had values between 8.5-9.5 and 9.5-10.5, respectively. Twelve percent of the participants had HbA1C level higher than 10.5. Correlation of fasting plasma glucose level and HbA1C was also studied and found that correlation coefficient came

  12. Patterns of glycemic control using glycosylated hemoglobin in diabetics.

    Science.gov (United States)

    Kahlon, Arunpreet Singh; Pathak, Rambha

    2011-07-01

    Till now estimation of blood glucose is the highly effective method for diagnosing diabetes mellitus but it provides a short-term picture of control. More evidence is required to prove that plasma glucose and glycosylated hemoglobin levels together gives a better estimate of glycemic control and compliance with treatment. Indian diabetes risk score (IDRS) is a simplified screening tool for identifying undiagnosed diabetic subjects, requires minimum time, and effort and can help to considerably reduce the costs of screening. To study patterns of glycemic control using glycosylated hemoglobin in diabetic patients. To find out correlation between levels of plasma glucose and glycosylated hemoglobin in diabetics and to calculate IDRS of the study population. A cross sectional study was conducted among 300 known diabetic patients attending outpatient department of a rural medical college in Haryana, India. Following standard procedures and protocols FPG and glycosylated hemoglobin were measured to find out a pattern of glycemic control in them after taking their written and informed consent. A correlation between the levels of glycosylated hemoglobin and fasting blood glucose was also calculated. These patients were made to fill a performa and their demographic and clinical risk factors were noted and based on this, their IDRS was calculated. This was done to validate the IDRS in Indian rural population. Fifty-two percent of the population had fasting plasma glucose level between 125-150 mg/dl, 21% had this level between 151-175 mg/dl. Thirteen percent of the study subjects had HbA1C between 6.5-7.5, more than half (57.3%) had this value between 7.5-8.5, 12% and 18% had values between 8.5-9.5 and 9.5-10.5, respectively. Twelve percent of the participants had HbA1C level higher than 10.5. Correlation of fasting plasma glucose level and HbA1C was also studied and found that correlation coefficient came out to be .311. This correlation was found to be statistically

  13. Molecular basis for the presence of glycosylated onco-foetal fibronectin in oral carcinomas

    DEFF Research Database (Denmark)

    Wandall, Hans H; Dabelsteen, Sally; Sørensen, Jens Ahm

    2007-01-01

    spliced IIICS region. Using cell culture experiments, immunohistochemical staining of primary tissue, and RT-PCR of tumour cells isolated by laser capture techniques we have examined the molecular basis for the production of GOF in oral carcinomas. Immuno-histochemical investigation confirmed the stromal......Glycosylated onco-foetal fibronectin (GOF) deposited in the stroma of oral squamous cell carcinomas correlates with survival. One of the two polypeptide GalNAc-transferases, GalNAc-T3 or GalNAc-T6, is required for the biosynthesis of GOF by the initiation of a unique O-glycan in the alternative...... deposition of GOF in oral carcinomas. However, neither GalNAc-T3 nor GalNAc-T6 could be detected in stromal fibroblasts. In contrast both transferases were present in the oral squamous carcinoma cells, suggesting that GOF is produced by the oral cancer cells and not only the stromal cells. RT-PCR analysis...

  14. TNF-α levels in cancer patients relate to social variables

    Science.gov (United States)

    Marucha, Phillip T.; Crespin, Timothy R.; Shelby, Rebecca A.; Andersen, Barbara L.

    2008-01-01

    Tumor necrosis factor-α (TNF-α) is an important cytokine associated with tumor regression and increased survival time for cancer patients. Research evidence relates immune factors (e.g., natural killer (NK) cell counts, NK cell lysis, lymphocyte profile, and lymphocyte proliferation) to the frequency and quality of social relations among cancer patients. We hypothesized that disruptions in social relations would be associated with lower TNF-α responses, and conversely, that reports of positive changes in social relations correlate with stronger responses. A prospective design measured changes in social activity and relationship satisfaction with a partner in 44 breast cancer patients at the time of cancer diagnosis, and initial surgery and 12 months later. Results indicated that patients reporting increased social activities or satisfaction exhibited stronger stimulated TNF-α responses. This is the first study to link changes in patient social relations with a cancer-relevant immune variable. PMID:15890493

  15. Treatment Related Cardiac Toxicity in Patients Treated for Breast Cancer

    National Research Council Canada - National Science Library

    Marks, Lawrence B

    2006-01-01

    Purpose: To determine the incidence dose/time-dependence and functional significance of regional cardiac perfusion abnormalities in patients with left-sided breast cancer treated with radiation therapy (RT...

  16. Diet-related cancer and prevention using anticarcinogens

    African Journals Online (AJOL)

    Administrator

    B and C infections in the causation of liver cancer. (Turner ..... Provitamins and vitamins (β- carotene, Vit.C, VitE, polyphenols ,including epigallocatechin gallate and various ..... Farombi EO, Tahnteng JG, Agboola O, Nwankwo JO, Emerole G.O.

  17. The management of breast cancer-related lymphoedema

    African Journals Online (AJOL)

    If BCRL is not detected and treated in its early stages, it becomes chronic and ... breast cancer diagnosis and treatment; however, it may occur at any stage during the .... dermatological problems are important to minimise the risk of infection.

  18. Meat-related compounds and colorectal cancer risk by anatomical subsite.

    Science.gov (United States)

    Miller, Paige E; Lazarus, Philip; Lesko, Samuel M; Cross, Amanda J; Sinha, Rashmi; Laio, Jason; Zhu, Jay; Harper, Gregory; Muscat, Joshua E; Hartman, Terryl J

    2013-01-01

    Since meat may be involved in the etiology of colorectal cancer, associations between meat-related compounds were examined to elucidate underlying mechanisms in a population-based case-control study. Participants (989 cases/1,033 healthy controls) completed a food frequency questionnaire with a meat-specific module. Multivariable logistic regression was used to examine associations between meat variables and colorectal cancer; polytomous logistic regression was used for subsite-specific analyses. The following significant positive associations were observed for meat-related compounds: 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal, distal colon, and rectal tumors; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and colorectal and colon cancer tumors; nitrites/nitrates and proximal colon cancer; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rectal cancer; and benzo[a]pyrene and rectal cancer (P-trends cancer and pan-fried red meat and colorectal cancer were found (P-trends cancer; and well-done/charred poultry and colorectal, colon, and proximal colon tumors (P-trends nitrates may be involved in colorectal cancer etiology. Further examination into the unexpected inverse associations between poultry and colorectal cancer is warranted.

  19. Goal setting in cancer rehabilitation and relation to quality of life among women with gynaecological cancer

    DEFF Research Database (Denmark)

    Holt, Kamila A; Mogensen, Ole; Jensen, Pernille T

    2015-01-01

    BACKGROUND: Rehabilitation should be integrated in the routine cancer care of women treated for gynaecological cancers. Goal setting is expected to facilitate the process through patient involvement and motivation. Our knowledge about goal setting in cancer rehabilitation is, however, sparse...... and emotional categories were the second and third most frequent among patients with endometrial and ovarian cancer. Sexual issues were dominant among the cervical cancer patients. Regression analysis showed significant association between quality of life scores and goal setting within the social and emotional...

  20. Breast cancer literacy and health beliefs related to breast cancer screening among American Indian women.

    Science.gov (United States)

    Roh, Soonhee; Burnette, Catherine E; Lee, Yeon-Shim; Jun, Jung Sim; Lee, Hee Yun; Lee, Kyoung Hag

    2018-08-01

    The purpose of this article is to examine the health beliefs and literacy about breast cancer and their relationship with breast cancer screening among American Indian (AI) women. Using the Health Belief Model (HBM) and hierarchical logistic regression with data from a sample of 286 AI female adults residing in the Northern Plains, we found that greater awareness of breast cancer screening was linked to breast cancer screening practices. However, perceived barriers, one of the HBM constructs, prevented such screening practices. This study suggested that culturally relevant HBM factors should be targeted when developing culturally sensitive breast cancer prevention efforts.

  1. Estimation of baseline lifetime risk of developed cancer related to radiation exposure in China

    International Nuclear Information System (INIS)

    Li Xiaoliang; Niu Haowei; Sun Quanfu; Ma Weidong

    2011-01-01

    Objective: To introduce the general international method for estimation of lifetime risk of developed cancer, and to estimate the lifetime risk baseline values of several kinds of cancers related to radiation exposures in China. Methods: The risk estimation was based on the data from Chinese Cancer Registry Annual Report (2010) and China Population and Employment Statistics Yearbook (2009), and made according to the method previously published by National Cancer Institute (NCI) in USA. Results: The lifetime risk of all cancer in China in 2007 was estimated to be 27.77%, that of lung cancer 5.96%, that of breast cancer for female 3.34%, that of all leukemia 0.14%, that of thyroid cancer 0.37%. The lifetime risks of all cancer were estimated to be 32.74% for males and 24.73% for females, and that was 36.47% for urban residents and 26.79% for rural people. Conclusions: The lifetime risk of all cancer for males in 2007 was about 1.25 times as much as that for females. The value of all cancer for urban residents was about 1.35 times as much as that for rural residents. The lifetime risk of developed cancers in 2007 in China is lower than that in the developed countries,such as Japan. (authors)

  2. Cancer risk in relation to serum copper levels.

    Science.gov (United States)

    Coates, R J; Weiss, N S; Daling, J R; Rettmer, R L; Warnick, G R

    1989-08-01

    A nested, matched case-control study was conducted to assess the relationship between serum levels of copper and the subsequent risk of cancer. One hundred thirty-three cases of cancer were identified during 1974-1984 among 5000 members of a northwest Washington State employee cohort from whom serum specimens had been previously obtained and stored. Two hundred forty-one controls were selected at random from the cohort and were matched to the cases on the basis of age, sex, race, and date of blood draw. Serum copper levels were measured by atomic absorption spectrometry. Risk of a subsequent diagnosis of cancer was positively associated with serum copper levels, but only among those cases diagnosed within 4 years of the time the serum specimens were collected. Among cases diagnosed more than 4 years after specimen collection, there was no consistent association between serum copper levels and risk. Adjustment for age, sex, race, occupational status, cigarette smoking, family history of cancer, alcohol consumption, and, among females, use of exogenous hormones had no appreciable effect on these relationships. The findings suggest that the presence of cancer may increase serum copper levels several years prior to its diagnosis. They are less supportive of the hypothesis that serum copper levels affect cancer risk.

  3. Employment and work-related issues in cancer survivors.

    Science.gov (United States)

    Mehnert, Anja

    2011-02-01

    Purpose of this systematic literature review was to identify current knowledge about employment in cancer survivors. Sixty-four studies met inclusion criteria that were original papers published between 01/2000 and 11/2009. Overall, 63.5% of cancer survivors (range 24-94%) returned to work. The mean duration of absence from work was 151 days. Factors significantly associated with a greater likelihood of being employed or return to work were perceived employer accommodation, flexible working arrangements, counseling, training and rehabilitation services, younger age and cancer sites of younger individuals, higher levels of education, male gender, less physical symptoms, lower length of sick leave and continuity of care. Cancer survivors had a significantly increased risk for unemployment, early retirement and were less likely to be re-employed. Between 26% and 53% of cancer survivors lost their job or quit working over a 72-month period post diagnosis. Between 23% and 75% of patients who lost their job were re-employed. A high proportion of patients experienced at least temporary changes in work schedules, work hours, wages and a decline in work ability compared to non-cancer groups. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Return to work and its relation to financial distress among Iranian cancer survivors.

    Science.gov (United States)

    Ghasempour, Mostafa; Rahmani, Azad; Davoodi, Arefeh; Sheikhalipour, Zahra; Ziaeei, Jamal Evazie; Abri, Fariba

    2015-01-01

    Return to work after treatment completion is important for both cancer survivors and society. Financial distress is one of the factors that may influence the return to work in cancer survivors. However, this relationship has not been well investigated. This study aimed to determine the rate of return to work and its relation to financial distress among Iranian cancer survivors. This descriptive-correlational study was undertaken among 165 cancer survivors who completed their initial treatments and had no signs of active cancer. The Return to Work questionnaire and Financial Distress/Financial Well-Being Scale were used for data collection. Data were analyzed using SPSS statistical software. After initial treatments, 120 cancer survivors (72%) had returned to work, of which 50 patients (42%) had returned to full-time work and 70 (58%) reduced their work hours and returned to part-time work. Cancer survivors also reported high levels of financial distress. In addition, the financial distress was lower among patients who had returned completely to work, in comparison to patients who had quit working for cancer-related reasons (p=0.001) or returned to work as part-time workers (p=0.001). The findings showed that a high percent of Iranian cancer survivors had not returned to their jobs or considerably reduced working hours after treatment completion. Accordingly, due to high levels of financial distress experienced by participants and its relation to return to work, designing rehabilitation programs to facilitate cancer survivor return to work should be considered.

  5. Structural differences between glycosylated, disulfide-linked heterodimeric Knob-into-Hole Fc fragment and its homodimeric Knob-Knob and Hole-Hole side products.

    Science.gov (United States)

    Kuglstatter, A; Stihle, M; Neumann, C; Müller, C; Schaefer, W; Klein, C; Benz, J

    2017-09-01

    An increasing number of bispecific therapeutic antibodies are progressing through clinical development. The Knob-into-Hole (KiH) technology uses complementary mutations in the CH3 region of the antibody Fc fragment to achieve heavy chain heterodimerization. Here we describe the X-ray crystal structures of glycosylated and disulfide-engineered heterodimeric KiH Fc fragment and its homodimeric Knob-Knob and Hole-Hole side products. The heterodimer structure confirms the KiH design principle and supports the hypothesis that glycosylation stabilizes a closed Fc conformation. Both homodimer structures show parallel Fc fragment architectures, in contrast to recently reported crystal structures of the corresponding aglycosylated Fc fragments which in the absence of disulfide mutations show an unexpected antiparallel arrangement. The glycosylated Knob-Knob Fc fragment is destabilized as indicated by variability in the relative orientation of its CH3 domains. The glycosylated Hole-Hole Fc fragment shows an unexpected intermolecular disulfide bond via the introduced Y349C Hole mutation which results in a large CH3 domain shift and a new CH3-CH3 interface. The crystal structures of glycosylated, disulfide-linked KiH Fc fragment and its Knob-Knob and Hole-Hole side products reported here will facilitate further design of highly efficient antibody heterodimerization strategies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Oxidative DNA as related to cancer and aging

    International Nuclear Information System (INIS)

    Ames, B.N.

    1987-01-01

    DNA damage in man can result from a variety of endogenous processes. Of particular importance as endogenous processes may be metabolic pathways that generate oxygen radicals and other reactive oxygen species. Oxygen radicals have been shown to produce DNA base damage and strand breaks. Two products that are formed in DNA in vitro by chemical oxidation or ionizing radiation (and oxidative mutagen) are thymine glycol and hydroxymethyl-uracil, both oxidation products of thymine. Specific mammalian DNA repair systems are known to excise these lesions from DNA in vitro. The authors' laboratory has recently reported the identification, in both human and rat urine, of thymine glycol, thymidine glycol, and hydroxymethyluracil. They now have considerable evidence that these products are derived from the repair of oxidized DNA. The total output of these three compounds represents the formation of about 1,000 oxidized thymine residues per cell per day in man. Since these products are only three of a considerable number of types of oxidative DNA damage products described by radiobiologists, there are likely to be several thousand oxidative DNA hits per cell per day in man. Rats, which have a higher specific metabolic rate and a shorter life span, excrete about 15 times more thymine glycol, thymidine glycol, and hydroxymethyluracil per kilogram body weight. The authors also describe new methods for measuring the levels, which are considerable, of hydrogen peroxide and lipid hydroperoxides in normal plasma and tissues. These non-invasive assays of DNA and other oxidation products may allow the direct testing of current theories that relate oxidative metabolism to the processes of cancer and aging in man

  7. Introduction of a glycosylation site in the constant region decreases the aggregation of adalimumab Fab.

    Science.gov (United States)

    Nakamura, Hitomi; Oda-Ueda, Naoko; Ueda, Tadashi; Ohkuri, Takatoshi

    2018-06-18

    The production of therapeutic monoclonal antibodies is costly; therefore, antigen-binding fragments (Fabs) can be used instead. However, their tendency toward aggregation can reduce the half-life in the plasma and the therapeutic effectiveness. To examine the effect of glycosylation on the properties of the Fab of a therapeutic antibody, an N-glycosylation site was introduced at position 178 of the H-chain constant region of adalimumab Fab through site-directed mutagenesis of L178 N (H:L178 N Fab), and then H:L178 N Fab was expressed in Pichia pastoris. SDS-PAGE analysis with treatment of N-glycosidase F or periodic acid-Schiff reagent showed that H:L178 N Fab contained a relatively low glycan level. Moreover, the H:L178 N mutation did not decrease the binding activity and thermal stability of Fab, and H:L178 N Fab was more resistant to protease digestion than wild-type Fab. The aggregation of Fab induced by pH-shift stress was measured by monitoring the optical density at 350 nm. Although the wild-type Fab showed a large increase in optical density with an increase of protein concentration, no such increase of turbidity during aggregation was found in H:L178 N Fab. These results demonstrated that glycosylation at position 178 of the H-chain constant region of adalimumab Fab can prevent protein aggregation, and therefore serve as a potentially effective platform for drug development. Copyright © 2018. Published by Elsevier Inc.

  8. Return to work after early-stage breast cancer : A cohort study into the effects of treatment and cancer-related symptoms

    NARCIS (Netherlands)

    Balak, Fulya; Roelen, Corne A. M.; Koopmans, Petra C.; ten Berge, Elike E.; Groothoff, Johan W.

    Introduction Earlier diagnosis and better treatment have increased the survival rates of cancer patients. This warrants research on return to work of cancer survivors. What is the return to work rate following early-stage breast cancer? What is the effect of the type of treatment and cancer-related

  9. Excess breast cancer risk in first degree relatives of CHEK2∗1100delC positive familial breast cancer cases

    NARCIS (Netherlands)

    Adank, Muriel A.; Verhoef, Senno; Oldenburg, Rogier A.; Schmidt, Marjanka K.; Hooning, Maartje J.; Martens, John W. M.; Broeks, Annegien; Rookus, Matti; Waisfisz, Quinten; Witte, Birgit I.; Jonker, Marianne A.; Meijers-Heijboer, Hanne

    2013-01-01

    The CHEK2∗1100delC mutation confers a relative risk of two for breast cancer (BC) in the general population. This study aims to explore the excess cancer risk due to the CHEK2∗1100delC mutation within a familial non-BRCA1/2 breast cancer setting. Cancer incidences were compared between first degree

  10. Do Cancer-Related Beliefs Influence the Severity, Incidence, and Persistence of Psychological Symptoms?

    Science.gov (United States)

    Desautels, Caroline; Trudel-Fitzgerald, Claudia; Ruel, Sophie; Ivers, Hans; Savard, Josée

    Previous studies have suggested that negative beliefs about cancer may impair patients' psychological well-being, but only a few of these studies focused on specific psychological symptoms, and many were cross-sectional. The aim of this study was to investigate longitudinally the relationship of cancer-related cognitions with the severity, incidence, and persistence of anxiety, fear of cancer recurrence, depression, and insomnia symptoms during an 18-month period. Patients scheduled to undergo surgery for cancer (N = 962) completed a questionnaire assessing cancer-related cognitions at baseline (T1), the Hospital Anxiety and Depression Scale, the severity subscale of the Fear of Cancer Recurrence Inventory, and the Insomnia Severity Index at baseline (T1) and 2 (T2), 6 (T3), 10 (T4), 14 (T5), and 18 (T6) months later. Group × time factorial analyses using mixed models revealed that participants endorsing more negative cancer-related cognitions consistently reported more severe symptoms throughout the 18-month period. Logistic regression analyses suggested that endorsing more negative cancer-related cognitions at T1 significantly increased incidence and persistence rates of clinical levels of psychological symptoms. These findings suggest that the endorsement of negative cancer-related beliefs at the perioperative period influences the longitudinal evolution of anxiety, fear of cancer recurrence, depression, and insomnia symptoms in the following months. These results highlight the relevance of using cognitive restructuring early during the cancer care trajectory to potentially revise erroneous beliefs about cancer and prevent the incidence and persistence of psychological disturbances over time.

  11. Macrocyclic bis-thioureas catalyze stereospecific glycosylation reactions.

    Science.gov (United States)

    Park, Yongho; Harper, Kaid C; Kuhl, Nadine; Kwan, Eugene E; Liu, Richard Y; Jacobsen, Eric N

    2017-01-13

    Carbohydrates are involved in nearly all aspects of biochemistry, but their complex chemical structures present long-standing practical challenges to their synthesis. In particular, stereochemical outcomes in glycosylation reactions are highly dependent on the steric and electronic properties of coupling partners; thus, carbohydrate synthesis is not easily predictable. Here we report the discovery of a macrocyclic bis-thiourea derivative that catalyzes stereospecific invertive substitution pathways of glycosyl chlorides. The utility of the catalyst is demonstrated in the synthesis of trans-1,2-, cis-1,2-, and 2-deoxy-β-glycosides. Mechanistic studies are consistent with a cooperative mechanism in which an electrophile and a nucleophile are simultaneously activated to effect a stereospecific substitution reaction. Copyright © 2017, American Association for the Advancement of Science.

  12. Cancer-Related Stress and Complementary and Alternative Medicine: A Review

    Directory of Open Access Journals (Sweden)

    Kavita D. Chandwani

    2012-01-01

    Full Text Available A cancer diagnosis elicits strong psychophysiological reactions that characterize stress. Stress is experienced by all patients but is usually not discussed during patient-healthcare professional interaction; thus underdiagnosed, very few are referred to support services. The prevalence of CAM use in patients with history of cancer is growing. The purpose of the paper is to review the aspects of cancer-related stress and interventions of commonly used complementary and alternative techniques/products for amelioration of cancer-related stress. Feasibility of intervention of several CAM techniques and products commonly used by cancer patients and survivors has been established in some cancer populations. Efficacy of some CAM techniques and products in reducing stress has been documented as well as stress-related symptoms in patients with cancer such as mindfulness-based stress reduction, yoga, Tai Chi Chuan, acupuncture, energy-based techniques, and physical activity. Much of the research limitations include small study samples and variety of intervention length and content. Efficacy and safety of many CAM techniques and some herbs and vitamin B and D supplements need to be confirmed in further studies using scientific methodology. Several complementary and alternative medicine therapies could be integrated into standard cancer care to ameliorate cancer-related stress.

  13. Employment status and work-related difficulties in lung cancer survivors compared with the general population.

    Science.gov (United States)

    Kim, Young Ae; Yun, Young Ho; Chang, Yoon Jung; Lee, Jongmog; Kim, Moon Soo; Lee, Hyun-Sung; Zo, Jae Ill; Kim, Jhingook; Choi, Yong Soo; Shim, Young Mog; Yoon, Seok-Jun

    2014-03-01

    To investigate the employment status of lung cancer survivors and the work-related problems they face. Although the number of lung cancer survivors is increasing, little is known about their employment and work-related issues. We enrolled 830 lung cancer survivors 12 months after lung cancer curative surgery (median time after diagnosis, 4.11 years) and 1000 volunteers from the general population. All participants completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30-item and a questionnaire that included items relating to their jobs. We used logistic regression analysis to identify independent predictors of unemployment. The employment rate of lung cancer survivors decreased from 68.6% at the time of diagnosis to 38.8% after treatment, which was significantly lower than the employment rate of the general population (63.5%; adjusted odds ratio = 2.31, 95% confidence interval: 1.66-3.22). The posttreatment unemployment rate was higher for women than for men. Among survivors, employment was inversely associated with older age, household income, number of comorbidities, and poor social functioning. Fatigue (78.6%) was the most common work-related problem reported by survivors. Lung cancer survivors experienced more difficulties in employment than did the general population. Age, monthly household income, number of comorbidities, and social functioning appear to be important factors influencing employment status. These findings suggest that lung cancer survivors need support to cope with the financial impact of cancer.

  14. The cost of lost productivity due to premature cancer-related mortality: an economic measure of the cancer burden.

    Science.gov (United States)

    Hanly, Paul A; Sharp, Linda

    2014-03-26

    Most measures of the cancer burden take a public health perspective. Cancer also has a significant economic impact on society. To assess this economic burden, we estimated years of potential productive life lost (YPPLL) and costs of lost productivity due to premature cancer-related mortality in Ireland. All cancers combined and the 10 sites accounting for most deaths in men and in women were considered. To compute YPPLL, deaths in 5-year age-bands between 15 and 64 years were multiplied by average working-life expectancy. Valuation of costs, using the human capital approach, involved multiplying YPPLL by age-and-gender specific gross wages, and adjusting for unemployment and workforce participation. Sensitivity analyses were conducted around retirement age and wage growth, labour force participation, employment and discount rates, and to explore the impact of including household production and caring costs. Costs were expressed in €2009. Total YPPLL was lower in men than women (men = 10,873; women = 12,119). Premature cancer-related mortality costs were higher in men (men: total cost = €332 million, cost/death = €290,172, cost/YPPLL = €30,558; women: total cost = €177 million, cost/death = €159,959, cost/YPPLL = €14,628). Lung cancer had the highest premature mortality cost (€84.0 million; 16.5% of total costs), followed by cancers of the colorectum (€49.6 million; 9.7%), breast (€49.4 million; 9.7%) and brain & CNS (€42.4 million: 8.3%). The total economic cost of premature cancer-related mortality in Ireland amounted to €509.5 million or 0.3% of gross domestic product. An increase of one year in the retirement age increased the total all-cancer premature mortality cost by 9.9% for men and 5.9% for women. The inclusion of household production and caring costs increased the total cost to €945.7 million. Lost productivity costs due to cancer-related premature mortality are significant. The higher premature mortality cost in males than

  15. Coding completeness and quality of relative survival-related variables in the National Program of Cancer Registries Cancer Surveillance System, 1995-2008.

    Science.gov (United States)

    Wilson, Reda J; O'Neil, M E; Ntekop, E; Zhang, Kevin; Ren, Y

    2014-01-01

    Calculating accurate estimates of cancer survival is important for various analyses of cancer patient care and prognosis. Current US survival rates are estimated based on data from the National Cancer Institute's (NCI's) Surveillance, Epidemiology, and End RESULTS (SEER) program, covering approximately 28 percent of the US population. The National Program of Cancer Registries (NPCR) covers about 96 percent of the US population. Using a population-based database with greater US population coverage to calculate survival rates at the national, state, and regional levels can further enhance the effective monitoring of cancer patient care and prognosis in the United States. The first step is to establish the coding completeness and coding quality of the NPCR data needed for calculating survival rates and conducting related validation analyses. Using data from the NPCR-Cancer Surveillance System (CSS) from 1995 through 2008, we assessed coding completeness and quality on 26 data elements that are needed to calculate cancer relative survival estimates and conduct related analyses. Data elements evaluated consisted of demographic, follow-up, prognostic, and cancer identification variables. Analyses were performed showing trends of these variables by diagnostic year, state of residence at diagnosis, and cancer site. Mean overall percent coding completeness by each NPCR central cancer registry averaged across all data elements and diagnosis years ranged from 92.3 percent to 100 percent. RESULTS showing the mean percent coding completeness for the relative survival-related variables in NPCR data are presented. All data elements but 1 have a mean coding completeness greater than 90 percent as was the mean completeness by data item group type. Statistically significant differences in coding completeness were found in the ICD revision number, cause of death, vital status, and date of last contact variables when comparing diagnosis years. The majority of data items had a coding

  16. Electrospray Ionization Mass Spectrometric Analysis of Highly Reactive Glycosyl Halides

    Directory of Open Access Journals (Sweden)

    Lajos Kovács

    2012-07-01

    Full Text Available Highly reactive glycosyl chlorides and bromides have been analysed by a routine mass spectrometric method using electrospray ionization and lithium salt adduct-forming agents in anhydrous acetonitrile solution, providing salient lithiated molecular ions [M+Li]+, [2M+Li]+ etc. The role of other adduct-forming salts has also been evaluated. The lithium salt method is useful for accurate mass determination of these highly sensitive compounds.

  17. Glycosyl azide-a novel substrate for enzymatic transgycosylations

    Czech Academy of Sciences Publication Activity Database

    Fialová, Pavla; Carmona, A. T.; Robina, I.; Ettrich, R.; Sedmera, Petr; Přikrylová, Věra; Hušáková, Lucie; Křen, Vladimír

    2005-01-01

    Roč. 46, - (2005), s. 8715-8718 ISSN 0040-4039 R&D Projects: GA ČR GA203/05/0172; GA MŠk OC D25.002 Grant - others:GA KONTAKT 1862/04 Institutional research plan: CEZ:AV0Z50200510 Keywords : enzyme catalysis * glycosyl azide * molecular modelling Subject RIV: EE - Microbiology, Virology Impact factor: 2.477, year: 2005

  18. Enhanced SCAP glycosylation by inflammation induces macrophage foam cell formation.

    Directory of Open Access Journals (Sweden)

    Chao Zhou

    Full Text Available Inflammatory stress promotes foam cell formation by disrupting LDL receptor feedback regulation in macrophages. Sterol Regulatory Element Binding Proteins (SREBPs Cleavage-Activating Protein (SCAP glycosylation plays crucial roles in regulating LDL receptor and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoAR feedback regulation. The present study was to investigate if inflammatory stress disrupts LDL receptor and HMGCoAR feedback regulation by affecting SCAP glycosylation in THP-1 macrophages. Intracellular cholesterol content was assessed by Oil Red O staining and quantitative assay. The expression of molecules controlling cholesterol homeostasis was examined using real-time quantitative RT-PCR and Western blotting. The translocation of SCAP from the endoplasmic reticulum (ER to the Golgi was detected by confocal microscopy. We demonstrated that exposure to inflammatory cytokines increased lipid accumulation in THP-1 macrophages, accompanying with an increased SCAP expression even in the presence of a high concentration of LDL. These inflammatory cytokines also prolonged the half-life of SCAP by enhancing glycosylation of SCAP due to the elevated expression of the Golgi mannosidase II. This may enhance translocation and recycling of SCAP between the ER and the Golgi, escorting more SREBP2 from the ER to the Golgi for activation by proteolytic cleavages as evidenced by an increased N-terminal of SREBP2 (active form. As a consequence, the LDL receptor and HMGCoAR expression were up-regulated. Interestingly, these effects could be blocked by inhibitors of Golgi mannosidases. Our results indicated that inflammation increased native LDL uptake and endogenous cholesterol de novo synthesis, thereby causing foam cell formation via increasing transcription and protein glycosylation of SCAP in macrophages. These data imply that inhibitors of Golgi processing enzymes might have a potential vascular-protective role in prevention of atherosclerotic foam

  19. Reduced apolipoprotein glycosylation in patients with the metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Olga V Savinova

    Full Text Available The purpose of this study was to compare the apolipoprotein composition of the three major lipoprotein classes in patients with metabolic syndrome to healthy controls.Very low density (VLDL, intermediate/low density (IDL/LDL, hereafter LDL, and high density lipoproteins (HDL fractions were isolated from plasma of 56 metabolic syndrome subjects and from 14 age-sex matched healthy volunteers. The apolipoprotein content of fractions was analyzed by one-dimensional (1D gel electrophoresis with confirmation by a combination of mass spectrometry and biochemical assays.Metabolic syndrome patients differed from healthy controls in the following ways: (1 total plasma--apoA1 was lower, whereas apoB, apoC2, apoC3, and apoE were higher; (2 VLDL--apoB, apoC3, and apoE were increased; (3 LDL--apoC3 was increased, (4 HDL--associated constitutive serum amyloid A protein (SAA4 was reduced (p<0.05 vs. controls for all. In patients with metabolic syndrome, the most extensively glycosylated (di-sialylated isoform of apoC3 was reduced in VLDL, LDL, and HDL fractions by 17%, 30%, and 25%, respectively (p<0.01 vs. controls for all. Similarly, the glycosylated isoform of apoE was reduced in VLDL, LDL, and HDL fractions by 15%, 26%, and 37% (p<0.01 vs. controls for all. Finally, glycosylated isoform of SAA4 in HDL fraction was 42% lower in patients with metabolic syndrome compared with controls (p<0.001.Patients with metabolic syndrome displayed several changes in plasma apolipoprotein composition consistent with hypertriglyceridemia and low HDL cholesterol levels. Reduced glycosylation of apoC3, apoE and SAA4 are novel findings, the pathophysiological consequences of which remain to be determined.

  20. High cancer-related mortality in an urban, predominantly African-American, HIV-infected population.

    Science.gov (United States)

    Riedel, David J; Mwangi, Evelyn Ivy W; Fantry, Lori E; Alexander, Carla; Hossain, Mian B; Pauza, C David; Redfield, Robert R; Gilliam, Bruce L

    2013-04-24

    To determine mortality associated with a new cancer diagnosis in an urban, predominantly African-American, HIV-infected population. Retrospective cohort study. All HIV-infected patients diagnosed with cancer between 1 January 2000 and 30 June 2010 were reviewed. Mortality was examined using Kaplan-Meier estimates and Cox proportional hazards models. There were 470 cases of cancer among 447 patients. Patients were predominantly African-American (85%) and male (79%). Non-AIDS-defining cancers (NADCs, 69%) were more common than AIDS-defining cancers (ADCs, 31%). Cumulative cancer incidence increased significantly over the study period. The majority (55.9%) was taking antiretroviral therapy (ART) at cancer diagnosis or started afterward (26.9%); 17.2% never received ART. Stage 3 or 4 cancer was diagnosed in 67%. There were 226 deaths during 1096 person years of follow-up, yielding an overall mortality rate of 206 per 1000 person years. The cumulative mortality rate at 30 days, 1 year, and 2 years was 6.5, 32.2, and 41.4%, respectively. Mortality was similar between patients on ART whether they started before or after the cancer diagnosis but was higher in patients who never received ART. In patients with a known cause of death, 68% were related to progression of the underlying cancer. In a large cohort of urban, predominantly African-American patients with HIV and cancer, many patients presented with late-stage cancer. There was substantial 30-day and 2-year mortality, although ART had a significant mortality benefit. Deaths were most often caused by progression of cancer and not from another HIV-related or AIDS-related event.

  1. Angiogenesis-Related Pathways in the Pathogenesis of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Aristotle Bamias

    2013-07-01

    Full Text Available Ovarian Cancer represents the most fatal type of gynecological malignancies. A number of processes are involved in the pathogenesis of ovarian cancer, especially within the tumor microenvironment. Angiogenesis represents a hallmark phenomenon in cancer, and it is responsible for tumor spread and metastasis in ovarian cancer, among other tumor types, as it leads to new blood vessel formation. In recent years angiogenesis has been given considerable attention in order to identify targets for developing effective anti-tumor therapies. Growth factors have been identified to play key roles in driving angiogenesis and, thus, the formation of new blood vessels that assist in “feeding” cancer. Such molecules include the vascular endothelial growth factor (VEGF, the platelet derived growth factor (PDGF, the fibroblast growth factor (FGF, and the angiopoietin/Tie2 receptor complex. These proteins are key players in complex molecular pathways within the tumor cell and they have been in the spotlight of the development of anti-angiogenic molecules that may act as stand-alone therapeutics, or in concert with standard treatment regimes such as chemotherapy. The pathways involved in angiogenesis and molecules that have been developed in order to combat angiogenesis are described in this paper.

  2. Detection of site specific glycosylation in proteins using flow cytometry†

    Science.gov (United States)

    Jayakumar, Deepak; Marathe, Dhananjay D.; Neelamegham, Sriram

    2009-01-01

    We tested the possibility that it is possible to express unique peptide probes on cell surfaces and detect site-specific glycosylation on these peptides using flow cytometry. Such development can enhance the application of flow cytometry to detect and quantify post-translational modifications in proteins. To this end, the N-terminal section of the human leukocyte glycoprotein PSGL-1 (P-selectin glycoprotein ligand-1) was modified to contain a poly-histidine tag followed by a proteolytic cleavage site. Amino acids preceding the cleavage site have a single O-linked glycosylation site. The recombinant protein called PSGL-1 (HT) was expressed on the surface of two mammalian cell lines, CHO and HL-60, using a lentiviral delivery approach. Results demonstrate that the N-terminal portion of PSGL-1 (HT) can be released from these cells by protease, and the resulting peptide can be readily captured and detected using cytometry-bead assays. Using this strategy, the peptide was immunoprecipitated onto beads bearing mAbs against either the poly-histidine sequence or the human PSGL-1. The carbohydrate epitope associated with the released peptide was detected using HECA-452 and CSLEX-1, monoclonal antibodies that recognize the sialyl Lewis-X epitope. Finally, the peptide released from cells could be separated and enriched using nickel chelate beads. Overall, such an approach that combines recombinant protein expression with flow cytometry, may be useful to quantify changes in site-specific glycosylation for basic science and clinical applications. PMID:19735085

  3. Glucosamine derived DISAL donors for stereoselective glycosylations under neutral conditions

    DEFF Research Database (Denmark)

    Grathe, S.; Thygesen, M.B.; Larsen, K.

    2005-01-01

    DISAL (methyl 3,5-dinitrosa/icylate) D-glcosyl, D-galactosyl, D-mannosyl, and L-quinovosyl donors have previously provided the efficient glycosylation of a range of substrates under either strictly neutral, mildly basic, or very mildly Lewis acidic (LiClO4) conditions. Herein we report the synthe......DISAL (methyl 3,5-dinitrosa/icylate) D-glcosyl, D-galactosyl, D-mannosyl, and L-quinovosyl donors have previously provided the efficient glycosylation of a range of substrates under either strictly neutral, mildly basic, or very mildly Lewis acidic (LiClO4) conditions. Herein we report...... the synthesis of new glucosamine DISAL donors, carrying N-TCP, -Troc, or -TFAc protecting groups, and their use in beta-(1,2-trans) selective glycosylations, primarily in NMP in the absence of any added Lewis acids, or in CH3NO2 with LiClO4. Finally, precise microwave heating proved effective in promoting...

  4. Frequency of colorectal cancer in healthy individual's relatives: A cross-sectional population-based study

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Zali

    2011-10-01

    Full Text Available Introduction: Family history of colorectal cancer has been shown to be related to the risk of developing colorectal cancer. This risk depends on the number of affected relatives and the age at diagnosis. In this study we aimed to estimate the frequency of a positive family history of colorectal cancer in a random sample from Tehran population. Materials and Methods: This study was a community-based cross-sectional survey conducted from May 2006 to December 2007 in Tehran province, Iran. A total of 5,500 peoples (age≥20 years drawn up randomly by random sampling according to postal codes and invited to participate in the study. All participants completed a detailed health data registry form on family history status of colorectal cancer. Results: The mean age of men with a positive family history was significantly different from men with negative family history. There was no significant difference between mean age of women responders with or without positive family history. Among all participants (n=5,500, 162 responders (2.9% had a history of colorectal cancer. Of 162, 67 responders (1.22% had one and 4(0.07% had two or more first-degree relative with colorectal cancer. Of 5,500 participants, 18 subjects (0.33% reported having two or more first-degree relative with colorectal cancer or one first-degree relative with colorectal cancer diagnosed at age <50 years. Four subjects (0.07% had three or more first-degree relative with colorectal cancer. Conclusion: Based on the findings, we estimate that more than 570,000 subjects in the Iran in the age group≥20 years have at least two to three times increased risk of developing colorectal cancer which should be identified and encourage to participate in screening and surveillance protocols of colorectal cancer.

  5. Relative Risk of Various Head and Neck Cancers among Different Blood Groups: An Analytical Study.

    Science.gov (United States)

    Singh, Khushboo; Kote, Sunder; Patthi, Basavaraj; Singla, Ashish; Singh, Shilpi; Kundu, Hansa; Jain, Swati

    2014-04-01

    Cancer is a unique disease characterized by abnormal growth of cells which have the ability to invade the adjacent tissues and sometimes even distant organs. The limited and contrasting evidence regarding the association of ABO blood groups with the different types of head and neck cancers in the Indian population warrants the need for the present study. To assess the relative risk of various Head & Neck cancers among different blood groups. Three hundred sixty two diagnosed cases of different type of head and neck cancers and 400 controls were selected from four hospitals of New Delhi, India. The information regarding the type of head and neck cancer was obtained from the case sheets of the patients regarding their socio demographic profile, dietary history using a structured performa. The information regarding type of cancer (cases only), ABO blood group was collected. Statistical Tests: The data was analysed using the SPSS 19 version. Chi square test and odd ratios were calculated. The level of significance was fixed at 5%. The O blood group was found to be most prevalent followed by B, A and AB among the cases as well as the controls. Oral cancer patients showed maximum number in blood group O followed by B, A and AB. Significant pattern of distribution was seen among the patients of esophageal cancer, laryngeal cancer and salivary gland cancer as well (p= 0.003, p=0.000 p=0.112 respectively. The present study reveals that there is an inherited element in the susceptibility or protection against different types of head and neck cancers. Blood group A was found to be a potential risk factor for the development of oral cancers, esophageal cancers and salivary gland cancers while blood group B was found to be a potential risk factor for laryngeal cancers.

  6. Relative Risk of Various Head and Neck Cancers among Different Blood Groups: An Analytical Study

    Science.gov (United States)

    Kote, Sunder; Patthi, Basavaraj; Singla, Ashish; Singh, Shilpi; Kundu, Hansa; Jain, Swati

    2014-01-01

    Background: Cancer is a unique disease characterized by abnormal growth of cells which have the ability to invade the adjacent tissues and sometimes even distant organs. The limited and contrasting evidence regarding the association of ABO blood groups with the different types of head and neck cancers in the Indian population warrants the need for the present study. Aim and Objective: To assess the relative risk of various Head & Neck cancers among different blood groups. Materials and Method: Three hundred sixty two diagnosed cases of different type of head and neck cancers and 400 controls were selected from four hospitals of New Delhi, India. The information regarding the type of head and neck cancer was obtained from the case sheets of the patients regarding their socio demographic profile, dietary history using a structured performa. The information regarding type of cancer (cases only), ABO blood group was collected. Statistical Tests: The data was analysed using the SPSS 19 version. Chi square test and odd ratios were calculated. The level of significance was fixed at 5%. Results: The O blood group was found to be most prevalent followed by B, A and AB among the cases as well as the controls. Oral cancer patients showed maximum number in blood group O followed by B, A and AB. Significant pattern of distribution was seen among the patients of esophageal cancer, laryngeal cancer and salivary gland cancer as well (p= 0.003, p=0.000 p=0.112 respectively. Conclusion: The present study reveals that there is an inherited element in the susceptibility or protection against different types of head and neck cancers. Blood group A was found to be a potential risk factor for the development of oral cancers, esophageal cancers and salivary gland cancers while blood group B was found to be a potential risk factor for laryngeal cancers. PMID:24959511

  7. Moisture-induced solid state instabilities in α-chymotrypsin and their reduction through chemical glycosylation

    Directory of Open Access Journals (Sweden)

    Solá Ricardo J

    2010-08-01

    Full Text Available Abstract Background Protein instability remains the main factor limiting the development of protein therapeutics. The fragile nature (structurally and chemically of proteins makes them susceptible to detrimental events during processing, storage, and delivery. To overcome this, proteins are often formulated in the solid-state which combines superior stability properties with reduced operational costs. Nevertheless, solid protein pharmaceuticals can also suffer from instability problems due to moisture sorption. Chemical protein glycosylation has evolved into an important tool to overcome several instability issues associated with proteins. Herein, we employed chemical glycosylation to stabilize a solid-state protein formulation against moisture-induced deterioration in the lyophilized state. Results First, we investigated the consequences of moisture sorption on the stability and structural conformation of the model enzyme α-chymotrypsin (α-CT under controlled humidity conditions. Results showed that α-CT aggregates and inactivates as a function of increased relative humidity (RH. Furthermore, α-CT loses its native secondary and tertiary structure rapidly at increasing RH. In addition, H/D exchange studies revealed that α-CT structural dynamics increased at increasing RH. The magnitude of the structural changes in tendency parallels the solid-state instability data (i.e., formation of buffer-insoluble aggregates, inactivation, and loss of native conformation upon reconstitution. To determine if these moisture-induced instability issues could be ameliorated by chemical glycosylation we proceeded to modify our model protein with chemically activated glycans of differing lengths (lactose and dextran (10 kDa. The various glycoconjugates showed a marked decrease in aggregation and an increase in residual activity after incubation. These stabilization effects were found to be independent of the glycan size. Conclusion Water sorption leads to

  8. Coping with pediatric cancer: strategies employed by children and their parents to manage cancer-related stressors during treatment.

    Science.gov (United States)

    Hildenbrand, Aimee K; Clawson, Kathleen J; Alderfer, Melissa A; Marsac, Meghan L

    2011-01-01

    Pediatric cancer patients and their families face significant physical, emotional, and psychosocial challenges. Few studies have investigated how children manage these challenges and how parents may help in the process. This qualitative study aimed to explore common cancer-related stressors for children and to examine child coping and parental assistance in coping with these stressors during treatment. Fifteen children undergoing cancer treatment and their parents participated in semistructured interviews. Four themes emerged capturing cancer-related stressors: cancer treatment/side effects, distressing emotions, disruption in daily routines, and social challenges. Six themes emerged regarding child coping strategies that were classified within an approach/avoidance coping framework. Approach coping strategies included the following: cognitive restructuring, relaxation, practical strategies, seeking social support, and emotional expression. Distraction was the only avoidant coping strategy. Parents tended to encourage approach coping strategies (eg, cognitive restructuring, social support). Within families, few coping strategies were reported (child: M = 1.47, SD = 0.99; parent: M = 3.33, SD = 1.18), suggesting that early family-based interventions teaching coping techniques for cancer-related stressors may be beneficial.

  9. Meat-Related Compounds and Colorectal Cancer Risk by Anatomical Subsite

    Science.gov (United States)

    Miller, Paige E.; Lazarus, Philip; Lesko, Samuel M.; Cross, Amanda J.; Sinha, Rashmi; Laio, Jason; Zhu, Jay; Harper, Gregory; Muscat, Joshua E.; Hartman, Terryl J.

    2012-01-01

    Since meat may be involved in the etiology of colorectal cancer, associations between meat-related compounds were examined to elucidate underlying mechanisms in a population-based case-control study. Participants (989 cases/1,033 healthy controls) completed a food frequency questionnaire with a meat-specific module. Multivariable logistic regression was used to examine associations between meat variables and colorectal cancer; polytomous logistic regression was used for subsite-specific analyses. The following significant positive associations were observed for meat-related compounds: 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and colorectal, distal colon, and rectal tumors; 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and colorectal and colon cancer tumors; nitrites/nitrates and proximal colon cancer; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and rectal cancer; and benzo[a]pyrene and rectal cancer (P-trends meat type, cooking method, and doneness preference, positive associations between red processed meat and proximal colon cancer and pan-fried red meat and colorectal cancer were found (P-trends nitrites, and nitrates may be involved in colorectal cancer etiology. Further examination into the unexpected inverse associations between poultry and colorectal cancer is warranted. PMID:23441608

  10. I-131 Dose Response for Incident Thyroid Cancers in Ukraine Related to the Chornobyl Accident

    OpenAIRE

    Brenner, Alina V.; Tronko, Mykola D.; Hatch, Maureen; Bogdanova, Tetyana I.; Oliynik, Valery A.; Lubin, Jay H.; Zablotska, Lydia B.; Tereschenko, Valery P.; McConnell, Robert J.; Zamotaeva, Galina A.; O?Kane, Patrick; Bouville, Andre C.; Chaykovskaya, Ludmila V.; Greenebaum, Ellen; Paster, Ihor P.

    2011-01-01

    Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case?control studies, and studies of prevalent cancers. Objective: To address this limitation, we evaluated the dose?response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study. Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who ...

  11. The Impact of Exercise on Cancer Mortality, Recurrence, and Treatment-Related Adverse Effects.

    Science.gov (United States)

    Cormie, Prue; Zopf, Eva M; Zhang, Xiaochen; Schmitz, Kathryn H

    2017-01-01

    The combination of an increasing number of new cancer cases and improving survival rates has led to a large and rapidly growing population with unique health-care requirements. Exercise has been proposed as a strategy to help address the issues faced by cancer patients. Supported by a growing body of research, major health organizations commonly identify the importance of incorporating exercise in cancer care and advise patients to be physically active. This systematic review comprehensively summarizes the available epidemiologic and randomized controlled trial evidence investigating the role of exercise in the management of cancer. Literature searches focused on determining the potential impact of exercise on 1) cancer mortality and recurrence and 2) adverse effects of cancer and its treatment. A total of 100 studies were reviewed involving thousands of individual patients whose exercise behavior was assessed following the diagnosis of any type of cancer. Compared with patients who performed no/less exercise, patients who exercised following a diagnosis of cancer were observed to have a lower relative risk of cancer mortality and recurrence and experienced fewer/less severe adverse effects. The findings of this review support the view that exercise is an important adjunct therapy in the management of cancer. Implications on cancer care policy and practice are discussed. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Health-related quality of life in rehabilitants with different cancer entities.

    Science.gov (United States)

    Lamprecht, J; Thyrolf, A; Mau, W

    2017-09-01

    The focus of the study is the analysis of changes in health-related quality of life in various cancer entities during and after an inpatient rehabilitation programme. In a multicentre longitudinal study, a total of 211 cancer patients (breast cancer: N = 84; prostate cancer: N = 90; colon cancer: N = 37) were asked about their quality of life (EORTC QLQ-C30; HADS) at the beginning, the end and 3 months after the end of the rehabilitation programme. In different domains of quality of life significant and mostly clinically relevant improvements were found during rehabilitation. The breast and prostate cancer patients improved most in emotional functioning, colon cancer patients in global quality of life. With regard to the severity of symptoms, the fatigue burden improved in breast and colon cancer patients, nausea in the prostate cancer patients. However, they are increases 3 months after rehabilitation. Functional burdens improved 3 months after the end of rehabilitation in the physical domain for all cancer patients. For breast cancer patients, emotional functioning decreased significantly 3 months after rehabilitation. An inpatient oncological rehabilitation programme can lead to an improvement in quality of life. © 2016 John Wiley & Sons Ltd.

  13. Crystallization and preliminary X-ray diffraction of human interleukin-7 bound to unglycosylated and glycosylated forms of its α-receptor

    Energy Technology Data Exchange (ETDEWEB)

    Wickham, Joseph Jr; Walsh, Scott T. R., E-mail: walsh.220@osu.edu [Department of Molecular and Cellular Biochemistry, Comprehensive Cancer Center, Ohio State University, 467 Hamilton Hall, 1645 Neil Avenue, Columbus, OH 43210 (United States)

    2007-10-01

    Bacterial and insect cell expression systems have been developed to produce unglycosylated and glycosylated forms of human interleukin-7 (IL-7) and the extracellular domain of its α receptor, IL-7Rα. We report the crystallization and X-ray diffraction of IL-7 complexes to both unglycosylated and glycosylated forms of the IL-7Rα to 2.7 and 3.0 Å, respectively. The interleukin-7 (IL-7) signaling pathway plays an essential role in the development, proliferation and homeostasis of T and B cells in cell-mediated immunity. Understimulation and overstimulation of the IL-7 signaling pathway leads to severe combined immunodeficiency, autoimmune reactions, heart disease and cancers. Stimulation of the IL-7 pathway begins with IL-7 binding to its α-receptor, IL-7Rα. Protein crystals of unglycosylated and glycosylated complexes of human IL-7–IL-7Rα extracellular domain (ECD) obtained using a surface entropy-reduction approach diffract to 2.7 and 3.0 Å, respectively. Anomalous dispersion methods will be used to solve the unglycosylated IL-7–IL-7Rα ECD complex structure and this unglycosylated structure will then serve as a model in molecular-replacement attempts to solve the structure of the glycosylated IL-7–α-receptor complex.

  14. Crystallization and preliminary X-ray diffraction of human interleukin-7 bound to unglycosylated and glycosylated forms of its α-receptor

    International Nuclear Information System (INIS)

    Wickham, Joseph Jr; Walsh, Scott T. R.

    2007-01-01

    Bacterial and insect cell expression systems have been developed to produce unglycosylated and glycosylated forms of human interleukin-7 (IL-7) and the extracellular domain of its α receptor, IL-7Rα. We report the crystallization and X-ray diffraction of IL-7 complexes to both unglycosylated and glycosylated forms of the IL-7Rα to 2.7 and 3.0 Å, respectively. The interleukin-7 (IL-7) signaling pathway plays an essential role in the development, proliferation and homeostasis of T and B cells in cell-mediated immunity. Understimulation and overstimulation of the IL-7 signaling pathway leads to severe combined immunodeficiency, autoimmune reactions, heart disease and cancers. Stimulation of the IL-7 pathway begins with IL-7 binding to its α-receptor, IL-7Rα. Protein crystals of unglycosylated and glycosylated complexes of human IL-7–IL-7Rα extracellular domain (ECD) obtained using a surface entropy-reduction approach diffract to 2.7 and 3.0 Å, respectively. Anomalous dispersion methods will be used to solve the unglycosylated IL-7–IL-7Rα ECD complex structure and this unglycosylated structure will then serve as a model in molecular-replacement attempts to solve the structure of the glycosylated IL-7–α-receptor complex

  15. Autoimmunity in differentiated thyroid cancer: significance and related clinical problems

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Rasmussen, Ase Krogh

    2011-01-01

    Coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune diseases could represent a mere coincidence due to the frequent occurrence of autoimmunity, but there may also be a pathological and causative link between the two conditions. The coincidence of DTC with Hashimoto's disease...... has been variably reported at between 0.5 and 22.5% and of DTC with Graves' disease between 0 and 9.8%. In this review available evidence for thyroid autoimmunity in DTC is summarized and it is concluded that thyroid cancer does coexist with thyroid autoimmunity, implying that patients treated...... TgAb measurements may be used as a surrogate marker for recurrence of thyroid cancer during the long-term monitoring of DTC patients....

  16. Autoimmunity in differentiated thyroid cancer: significance and related clinical problems

    DEFF Research Database (Denmark)

    Feldt-Rasmussen, Ulla; Rasmussen, Ase Krogh

    2010-01-01

    Coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune diseases could represent a mere coincidence due to the frequent occurrence of autoimmunity, but there may also be a pathological and causative link between the two conditions. The coincidence of DTC with Hashimoto's disease...... has been variably reported at between 0.5 and 22.5% and of DTC with Graves' disease between 0 and 9.8%. In this review available evidence for thyroid autoimmunity in DTC is summarized and it is concluded that thyroid cancer does coexist with thyroid autoimmunity, implying that patients treated...... TgAb measurements may be used as a surrogate marker for recurrence of thyroid cancer during the long-term monitoring of DTC patients....

  17. Update on Management of Cancer-Related Cachexia.

    Science.gov (United States)

    Anderson, Lindsey J; Albrecht, Eliette D; Garcia, Jose M

    2017-01-01

    Cachexia is a metabolic syndrome driven by inflammation and characterized by loss of muscle with or without loss of fat mass. In cancer cachexia, the tumor burden and host response induce increased inflammation, decreased anabolic tone, and suppressed appetite leading to the clinical presentation of reduced body weight and quality of life (QOL). There is no approved treatment for cancer cachexia, and commonly used nutritional and anti-inflammatory strategies alone have proven ineffective for management of symptoms. Several other pharmacological agents are currently in development and have shown promise as a clinical strategy in early-phase trials. Recently, it has been proposed that multimodal strategies, with an anabolic focus, initiated early in the disease/treatment progression may provide the most therapeutic potential for symptom management. Here we review the data from recent clinical trials in cancer cachexia including pharmacological, exercise, and nutritional interventions.

  18. [Establishment of a comprehensive database for laryngeal cancer related genes and the miRNAs].

    Science.gov (United States)

    Li, Mengjiao; E, Qimin; Liu, Jialin; Huang, Tingting; Liang, Chuanyu

    2015-09-01

    By collecting and analyzing the laryngeal cancer related genes and the miRNAs, to build a comprehensive laryngeal cancer-related gene database, which differs from the current biological information database with complex and clumsy structure and focuses on the theme of gene and miRNA, and it could make the research and teaching more convenient and efficient. Based on the B/S architecture, using Apache as a Web server, MySQL as coding language of database design and PHP as coding language of web design, a comprehensive database for laryngeal cancer-related genes was established, providing with the gene tables, protein tables, miRNA tables and clinical information tables of the patients with laryngeal cancer. The established database containsed 207 laryngeal cancer related genes, 243 proteins, 26 miRNAs, and their particular information such as mutations, methylations, diversified expressions, and the empirical references of laryngeal cancer relevant molecules. The database could be accessed and operated via the Internet, by which browsing and retrieval of the information were performed. The database were maintained and updated regularly. The database for laryngeal cancer related genes is resource-integrated and user-friendly, providing a genetic information query tool for the study of laryngeal cancer.

  19. Relation between breast parenchymal pattern and breast cancer

    International Nuclear Information System (INIS)

    Kim, Kyeung Hee; Lee, Sung Yong; Bahk, Yong Whee

    1985-01-01

    Although the usefulness of mammography as a screening test for breast cancer is still in dispute, its use to patients over 50 years of age is valid. Since Wolfe first classified the breast parenchymal patterns of mammography into 4 patterns, many authors have adopted the criteria in studying the changes of the parenchymal patterns for certain ages and the risks for breast cancer of certain parenchymal patterns. Authors reviewed 49 cases of breast masses which diagnosed by mammography and by operation during the period from January 1978 to July 1983 at St. Mary Hospital, Catholic Medical College. The parenchymal tissue patterns were classified according to Wolfe into N1, P1, P2 and DY, Risk groups were classified into low risk group (N1, P1) and high group (P2, DY). On the basis of these criteria, benign and malignant disease were analyzed against the breast parenchymal patterns. The results and conclusions were as follows: 1. Age ranged from 16 years to 67 years with the most prevalent age being 4th and 5th decades. 2. Diagnoses were: fibroadenoma 17 cases, fibrous dysplasia 16 cases, ductal papilloma 3 cases, and cancer 13 cases. 3. Categorization of those 26 benign disease according to the Wolfe's criteria was: N1 6 cases, P1 10 cases, P2 9 cases and DY 11 cases. On the other hand, categorization of 13 cases of cancer was: N1 5 caes, P1 3 cases, P2 3 cases, and DY 2 cases. 4. Of 13 cases of cancer, 8 fell in the low risk group and remainder in the high risk group. There were no significant correlation between the parenchymal patterns and the incidence of breast cancer

  20. Similarities and Differences in the Glycosylation Mechanisms in Prokaryotes and Eukaryotes

    Directory of Open Access Journals (Sweden)

    Anne Dell

    2010-01-01

    Full Text Available Recent years have witnessed a rapid growth in the number and diversity of prokaryotic proteins shown to carry N- and/or O-glycans, with protein glycosylation now considered as fundamental to the biology of these organisms as it is in eukaryotic systems. This article overviews the major glycosylation pathways that are known to exist in eukarya, bacteria and archaea. These are (i oligosaccharyltransferase (OST-mediated N-glycosylation which is abundant in eukarya and archaea, but is restricted to a limited range of bacteria; (ii stepwise cytoplasmic N-glycosylation that has so far only been confirmed in the bacterial domain; (iii OST-mediated O-glycosylation which appears to be characteristic of bacteria; and (iv stepwise O-glycosylation which is common in eukarya and bacteria. A key aim of the review is to integrate information from the three domains of life in order to highlight commonalities in glycosylation processes. We show how the OST-mediated N- and O-glycosylation pathways share cytoplasmic assembly of lipid-linked oligosaccharides, flipping across the ER/periplasmic/cytoplasmic membranes, and transferring “en bloc” to the protein acceptor. Moreover these hallmarks are mirrored in lipopolysaccharide biosynthesis. Like in eukaryotes, stepwise O-glycosylation occurs on diverse bacterial proteins including flagellins, adhesins, autotransporters and lipoproteins, with O-glycosylation chain extension often coupled with secretory mechanisms.

  1. Childhood cancer and factors related to prolonged diagnostic intervals

    DEFF Research Database (Denmark)

    Ahrensberg, J M; Olesen, F; Hansen, R P

    2013-01-01

    overleveringen til hospitalet var af betydning for hvor lang tid, der går fra lægesøgning til diagnose. Metode: Dansk populations-baseret studie. Data for 550 børn cancer diagnose (jan 2007-dec 2010) blev indsamlet vha spørgeskemaer til forældre (response-rate=69%) and praktiserende læger...... barnets symptomer som vage og ukarakteristiske i 25,4%; som alvorlige, men ikke cancer-relaterede i 50,0%; og som alarm symptom i 19,0% af tilfælde. Symptom tolkningen varierede med cancertype (p

  2. Prevention of HPV-Related Oral Cancer by Dentists: Assessing the Opinion of Dutch Dental Students.

    Science.gov (United States)

    Poelman, Marcella R; Brand, Henk S; Forouzanfar, Thymour; Daley, Ellen M; Jager, Derk H Jan

    2017-07-24

    The aim of this study is to assess dental students' opinions of the dentists' role in primary prevention of human papillomavirus (HPV)-related oral cancer using a cross-sectional web-based survey. A questionnaire, containing questions about knowledge of HPV and oral cancer, confidence in head and neck examination and role of the dentist in preventing HPV-related oral cancer, was sent to all students of the Academic Centre of Dentistry Amsterdam (n = 912). One hundred and twenty-six (n = 126) students completed the questionnaire. Significantly, more master students (75%) than bachelor students (54.3%) were aware that HPV is a causative factor for oral cancer. Master students had more knowledge of HPV than bachelor students, but knowledge about HPV vaccination was irrespective of the study phase. The majority of dental students agreed that it is important to discuss HPV vaccination with patients. Eighty-nine percent of the students think that more education about symptoms of oral cancer will increase screening for oral cancer. Development of a protocol for screening in dental practices was considered even more important. According to dental students, dentists should discuss HPV as a risk factor for oral cancer with patients. Future dentists are willing to be involved in both primary and secondary prevention of HPV-related oral cancer. Therefore, screening for oral cancer and education about HPV vaccination should be integral elements of the dental curriculum.

  3. Factors related to cancer information scanning and seeking behavior among high school students in Korea.

    Science.gov (United States)

    Kye, Su Yeon; Yun, E Hwa; Park, Keeho

    2012-01-01

    This paper aimed to determine the relationship between cancer information scanning and seeking experience of adolescents and cancer preventive behavior, perceived cancer risk, and levels of cancer- related knowledge. The study sample comprised 1,000 second-year students from 6 high schools: the general and vocational school systems were each represented by 1 boys', 1 girls', and 1 coeducational high school. In July 2011, trained researchers visited each classroom, explained the purpose of the study, distributed questionnaires to the students who agreed to participate, instructed them to complete the survey by self-reporting, and collected the completed questionnaires. The students who attended general high schools (as compared with vocational high schools), earned higher grades, consumed more vegetables, had a higher perceived cancer risk, and answered the cancer-related questions more correctly and had more cancer information scanning and seeking experience. These results reinforce the importance of cancer prevention health education. Furthermore, the results may help in preparing a strategy that enables people to acquire accurate cancer-related information easily and quickly.

  4. [Disease-free survival related factors in breast cancer].

    Science.gov (United States)

    Dávila-Arias, Cristina; Ocón, Olga; Fernández, Mariana F; Arrebola, Juan Pedro; Sánchez, María José; Aneiros, José; Torné, Pablo; Olea, Nicolás

    2014-10-07

    To evaluate the relationship between the clinical and pathological parameters of the primary tumor and disease-free survival (DFS) in a sample of hospital cases of invasive breast cancer. We performed a retrospective cohort study in 635 patients recruited at San Cecilio University Hospital in Granada (Spain) between 1994 and 2006. Information on the primary tumor and the outcomes of patients was collected by reviewing the medical records. Predictors of recurrence and/or metastasis and DFS (follow up of 3, 5 and 10 years) were analyzed by using Cox regression analysis. Multivariate models adjusted for age, tumor size, lymph nodal status, histological grade and estrogen and progesterone receptor expression showed a higher risk of recurrence and/or metastasis and lower DFS (adjusted relative risk, 95% confidence intervals) with tumor size (3 yrs: 3.00, 1.79-5.03; 5 yrs: 2.56, 1.65-3.98; 10 yrs: 2.16, 1.44-3.24), lymph nodal status (3 yrs: 4.58, 2.42-8.65; 5 yrs: 3.84, 2.35-6.30; 10 yrs: 3.08, 2.05-4.61), lymphovascular invasion (5 yrs: 1.88, 1.16-3.04; 10 yrs: 2.19, 1.43-3.35), multifocal and/or multicenter tumors (3 yrs: 2.69, 1.46-4.96; 5 yrs: 1.90, 1.08-3.35) and p53 protein expression (3 yrs: 2.03, 1.00-4.09). DFS was positively associated with an increased expression of progesterone receptor (3 yr: 0.48, 0.26-0.89; 5 yrs: 0.58, 0.35-0.97; 10 yrs: 0.59, 0.38-0.90). The biological characteristics of the primary tumor can be used to identify patients with distinctive prognoses and DFS, and could be helpful in making individual follow up strategies. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  5. Family history of cancer other than breast or ovarian cancer in first-degree relatives is associated with poor breast cancer prognosis.

    Science.gov (United States)

    Song, Jun-Long; Chen, Chuang; Yuan, Jing-Ping; Li, Juan-Juan; Sun, Sheng-Rong

    2017-04-01

    Whether a first-degree family history of others cancers (FHOC) than breast or ovarian cancer (BOC) is associated with breast cancer prognosis remains unknown. Thus, the aim of the present study was to clarify this issue. Women who were diagnosed with invasive breast cancer at the Renmin Hospital of Wuhan University from 2010 to 2013 were included in the study. The demographic and clinicopathological characteristics of these patients were extracted. FHOC was considered positive for any patient who had a relative who had been diagnosed with cancer other than BOC. Disease-free survival (DFS) was calculated based on the date of diagnosis. DFS was analyzed using the Cox proportional hazards model. A total of 434 breast cancer patients were included in this study. Among these patients, 61 (14.06%) had a positive FHOC in first-degree relatives. Patients with a positive FHOC tended to have HER2-positive breast cancer (p = 0.03). In the survival analysis, FHOC was associated with poor DFS in both univariate (HR = 2.21 (1.28-3.83), 95% CI: 1.28-3.83, p breast cancer patients with FHOC, especially in patients with luminal A subtype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. DNA methylation in Cosmc promoter region and aberrantly glycosylated IgA1 associated with pediatric IgA nephropathy.

    Directory of Open Access Journals (Sweden)

    Qiang Sun

    Full Text Available IgA nephropathy (IgAN is one of the most common glomerular diseases leading to end-stage renal failure. Elevation of aberrantly glycosylated IgA1 is a key feature of it. The expression of the specific molecular chaperone of core1ß1, 3galactosyl transferase (Cosmc is known to be reduced in IgAN. We aimed to investigate whether the methylation of CpG islands of Cosmc gene promoter region could act as a possible mechanism responsible for down-regulation of Cosmc and related higher secretion of aberrantly glycosylated IgA1in lymphocytes from children with IgA nephropathy. Three groups were included: IgAN children (n = 26, other renal diseases (n = 11 and healthy children (n = 13. B-lymphocytes were isolated and cultured, treated or not with IL-4 or 5-Aza-2'-deoxycytidine (AZA. The levels of DNA methylation of Cosmc promotor region were not significantly different between the lymphocytes of the three children populations (P = 0.113, but there were significant differences between IgAN lymphocytes and lymphocytes of the other two children populations after IL-4 (P<0.0001 or AZA (P<0.0001. Cosmc mRNA expression was low in IgAN lymphocytes compared to the other two groups (P<0.0001. The level of aberrantly glycosylated IgA1 was markedly higher in IgAN group compared to the other groups (P<0.0001. After treatment with IL-4, the levels of Cosmc DNA methylation and aberrantly glycosylated IgA1 in IgAN lymphocytes were remarkably higher than the other two groups (P<0.0001 with more markedly decreased Cosmc mRNA content (P<0.0001. After treatment with AZA, the levels in IgAN lymphocytes were decreased, but was still remarkably higher than the other two groups (P<0.0001, while Cosmc mRNA content in IgAN lymphocytes were more markedly increased than the other two groups (P<0.0001. The alteration of DNA methylation by IL-4 or AZA specifically correlates in IgAN lymphocytes with alterations in Cosmc mRNA expression and with the level of aberrantly glycosylated

  7. Implication for second primary cancer from visible oral and oropharyngeal premalignant lesions in betel-nut chewing related oral cancer.

    Science.gov (United States)

    Liu, Shyun-Yu; Feng, I-Jung; Wu, Yu-Wei; Chen, Ching-Yuan; Hsiung, Chao-Nan; Chang, Hsueh-Wei; Lin, Che-Yi; Chang, Min-Te; Yu, Hsi-Chien; Lee, Sheng-Yang; Yen, Ching-Yu

    2017-07-01

    Visible oral and oropharyngeal premalignant lesions may be used to monitor for a second primary oral cancer. To control for bias, we focused on the visible oral and oropharyngeal premalignant lesions of patients with oral cancer with a positive betel-nut chewing habit. Visible oral and oropharyngeal premalignant lesions that can predict second primary oral cancers were studied. Nine hundred ninety-seven patients with positive betel-nut chewing habits and oral cancer were enrolled in this retrospective cohort study. We analyzed the relevance of their visible oral and oropharyngeal premalignant lesion incidence and relative clinicopathological variables to the development of a second primary oral cancer. Second primary oral cancer risk was significantly higher in patients with positive visible oral and oropharyngeal premalignant lesions (P oral and oropharyngeal premalignant lesions make it a potentially valuable marker in follow-ups of patients with a positive betel-nut chewing habit with oral cancer, especially young patients with heterogeneous leukoplakia. © 2017 Wiley Periodicals, Inc.

  8. Advanced prostate cancer risk in relation to toenail selenium levels

    NARCIS (Netherlands)

    Geybels, M.S.; Verhage, B.A.J.; Schooten, F.J. van; Goldbohm, A.; Brandt, P.A. van den

    2013-01-01

    BACKGROUND: Selenium may prevent advanced prostate cancer (PCa), but most studies on this topic were conducted in populations with moderate to high selenium status. We investigated the association of toenail selenium, reflecting long-term selenium exposure, and advanced PCa risk in a population from

  9. Engaging Elements of Cancer-Related Digital Stories in Alaska

    Science.gov (United States)

    Cueva, Melany; Kuhnley, Regina; Revels, Laura; Schoenberg, Nancy E.; Lanier, Anne; Dignan, Mark

    2015-01-01

    The tradition of storytelling is an integral part of Alaska Native cultures that continues to be a way of passing on knowledge. Using a story-based approach to share cancer education is grounded in Alaska Native traditions and people’s experiences and has the potential to positively impact cancer knowledge, understandings, and wellness choices. Community health workers (CHWs) in Alaska created a personal digital story as part of a 5-day, in-person cancer education course. To identify engaging elements of digital stories among Alaska Native people, one focus group was held in each of three different Alaska communities with a total of 29 adult participants. After viewing CHWs’ digital stories created during CHW cancer education courses, focus group participants commented verbally and in writing about cultural relevance, engaging elements, information learned, and intent to change health behavior. Digital stories were described by Alaska focus group participants as being culturally respectful, informational, inspiring, and motivational. Viewers shared that they liked digital stories because they were short (only 2–3 min); nondirective and not preachy; emotional, told as a personal story and not just facts and figures; and relevant, using photos that showed Alaskan places and people. PMID:25865400

  10. Cancers related to Immunodeficiencies:Update and perspectives

    Directory of Open Access Journals (Sweden)

    Esmaeil Mortaz

    2016-09-01

    Full Text Available The life span of patients with primary and secondary immunodeficiency is increasing due to recent improvements in therapeutic strategies. Whilst, the incidence of primary immunodeficiencies (PIDs is 1:10.000 births, that of secondary immunodeficiencies is more common and are associated with post transplantation immune dysfunction or with immunosuppressive medication for human immunodeficiency virus (HIV or with human T-cell lymphotropic virus (HTLV infection.After infection, malignancy is the most prevalent cause of death in both children and adults with primary immunodeficiency disorders (PIDs. PIDs more often associated with cancer include common variable immunodeficiency (CVID, Wiskott Aldrich syndrome (WAS, ataxia-telangiectasia (AT and severe combined immunodeficiency (SCID. This suggests that a protective immune response against both infectious non-self (pathogens and malignant self-challenges (cancer exist. The increased incidence of cancer has been attributed to defective elimination of altered or transformed cells and/or defective immunity towards cancer cells. The concept of abberant immune surveillance occurring in PIDs is supported by evidence in mice and from patients undergoing immunosuppression after transplantation. Here, we discuss the importance of PID defects in the development of malignancies, the current limitations associated with molecular pathogenesis of these diseases and emphasize the need for further knowledge of how specific mutations can modulate the immune system to alter immunosurveillance and thereby play a key role in the etiology of malignancies in PID patients.

  11. Barriers and Motivators Related to Cervical and Breast Cancer Screening

    Directory of Open Access Journals (Sweden)

    M Bokaee

    2004-10-01

    Full Text Available Introduction: modern knowledge could protect against cancer for individuals in community with early stage and premalignat state. Screening of cancer is best instrument for early detection of malignancy. Between women’s cancers breast and cervical cancer have more incidence and mortality than other cancers . But could be prevented by simple and cheep screening programs. Despite specific statistics in Iran evidence shows that women’s participation in screening program is poor , so cancers are diagnosed in advanced stage. The purpose of this study was to identify major barriers and motivators for breast and cervical screening . Methods: This survey was a descriptive study in which 400 women participated in health and treatment centers in Yazd. Sampling method was done in two simple and random stages. Data was collected by inventory and questionnaire . Then data were analyzed by SPSS soft ware . Results: Findings showed that 80% of them never refereed to a health provider for clinical breast exam (C B E and only 3% of them did regularly C B E . 46% of them had never done pap smear and only 14.5 % of them did regularly pap smear. The findings showed that major motivators were as follow: advice of health’s personnel , using of contraceptive methods , and awareness of media. Also the major barriers were as follow : Not having knowledge of these exams , not having knowledge of the existence of these centers of education and practice , not having precious health problems , fear of examination , Embarrassment of examination and health providers not to teach them . to consider the most important barriers were propounded which showed that health education role to eliminate barriers for referring women for screening . Discussion: Based on the results of this sample , screening was the least expected . considering barriers and motivators observed it was revealed that health education was required for prevention of common women’s cancers. Also

  12. Relation between breast cancer mortality and screening effectiveness: systematic review of the mammography trials

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C

    2011-01-01

    The mammography screening trials have shown varying results. This could be because screening was better in some trials than in others at advancing the time of diagnosis. If so, more cancers would be identified in such trials relative to the control group, and fewer of the cancers would have reach...

  13. Malnutrition is associated with worse health-related quality of life in children with cancer

    NARCIS (Netherlands)

    Brinksma, Aeltsje; Sanderman, Robbert; Roodbol, Petrie F.; Sulkers, Esther; Burgerhof, Johannes G. M.; de Bont, Eveline S. J. M.; Tissing, Wim J. E.

    2015-01-01

    Malnutrition in childhood cancer patients has been associated with lower health-related quality of life (HRQOL). However, this association has never actually been tested. Therefore, we aimed to determine the association between nutritional status and HRQOL in children with cancer. In 104 children,

  14. Birth weight, childhood body mass index, and height in relation to mammographic density and breast cancer

    DEFF Research Database (Denmark)

    Andersen, Zorana Jovanovic; Baker, Jennifer Lyn; Bihrmann, Kristine

    2014-01-01

    High breast density, a strong predictor of breast cancer may be determined early in life. Childhood anthropometric factors have been related to breast cancer and breast density, but rarely simultaneously. We examined whether mammographic density (MD) mediates an association of birth weight, child...

  15. Nutrition-Related Cancer Prevention Cognitions and Behavioral Intentions: Testing the Risk Perception Attitude Framework

    Science.gov (United States)

    Sullivan, Helen W.; Beckjord, Ellen Burke; Finney Rutten, Lila J.; Hesse, Bradford W.

    2008-01-01

    This study tested whether the risk perception attitude framework predicted nutrition-related cancer prevention cognitions and behavioral intentions. Data from the 2003 Health Information National Trends Survey were analyzed to assess respondents' reported likelihood of developing cancer (risk) and perceptions of whether they could lower their…

  16. How to improve the implementation of guidelines on cancer-related thrombosis

    NARCIS (Netherlands)

    Debourdeau, Philippe; Beckers, Marielle; Gerome, Patrick; Durant, Cecile; Lacoin, Quitterie; Debourdeau, Antoine; Bancel, Dominique Farge

    Venous thromboembolism (VTE; defined by deep-vein thrombosis, central venous catheter-related thrombosis or pulmonary embolism) is a major therapeutic issue in cancer patients. VTE is reported in 15-20% of patients with cancer and is an independent prognostic factor and a leading cause of death. In

  17. Immediate Antiretroviral Therapy Reduces Risk of Infection-Related Cancer During Early HIV Infection

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; Neuhaus, Jacqueline; Babiker, Abdel G

    2016-01-01

    BACKGROUND:  In the Strategic Timing of Antiretroviral Treatment (START) study, immediate combination antiretroviral therapy (cART) initiation reduced cancer risk by 64%. We hypothesized that risk reduction was higher for infection-related cancer and determined by differences in CD4 cell counts a...

  18. Advice about Work-Related Issues to Peers and Employers from Head and Neck Cancer Survivors

    NARCIS (Netherlands)

    Dewa, Carolyn S.; Trojanowski, Lucy; Tamminga, Sietske J.; Ringash, Jolie; McQuestion, Maurene; Hoch, Jeffrey S.

    2016-01-01

    The purpose of this exploratory and descriptive study is to contribute to the sparse return-to-work literature on head and neck cancer (HNC) survivors. Interview participants were asked to reflect upon their work-related experience with cancer by answering two specific questions: (1) What advice

  19. Malnutrition is associated with worse health-related quality of life in children with cancer

    NARCIS (Netherlands)

    Brinksma, A.; Sanderman, Robbert; Roodbol, P.F.; Sulkers, E.; Burgerhof, J.G.M.; de Bont, E.S.J.M.; Tissing, W.J.E.

    2015-01-01

    Purpose: Malnutrition in childhood cancer patients has been associated with lower health-related quality of life (HRQOL). However, this association has never actually been tested. Therefore, we aimed to determine the association between nutritional status and HRQOL in children with cancer. Methods:

  20. Nutritional Information Provision to Cancer Patients and Their Relatives Can Promote Dietary Behavior Changes Independent of Nutritional Information Needs

    NARCIS (Netherlands)

    Veen, van Merel R.; Winkels, Renate M.; Janssen, Silvie H.M.; Kampman, Ellen; Beijer, Sandra

    2018-01-01

    We investigated whether obtaining nutritional information influences reported changes in dietary behavior in cancer survivors and their relatives and whether nutritional information needs influence this association. We included 239 cancer survivors and their relatives, recruited from an online panel

  1. Health-related Quality of Life after complex rectal surgery for primary advanced rectal cancer and locally recurrent rectal cancer

    DEFF Research Database (Denmark)

    Thaysen, Henriette Vind

    2013-01-01

    postoperative morbidity, Health-related Quality of Life (HRQoL) is an important issue. The overall aim of this thesis was therefore to evaluate HRQoL in patients with PARC and LRRC treated with COMP-RCS and curative intent. In study I a review of the literature was undertaken to provide an overview of HRQo......Advances in the treatment of rectal cancer, have made it possible to perform complex rectal cancer surgery (COMP-RCS) with curative intent in patients with primary advanced rectal caner (PARC) and local recurrent rectal cancer (LRRC). Due to the complexity of the treatment and its high...... in the study was 164 (86%) patients treated with standard rectal cancer surgery (STAN-RCS). The Danish version showed satisfactory psychometric properties for the scales concerning body image, sexual functioning, male sexual problems and defecations problems. Reduced psychometric properties were found...

  2. Abnormalities in alternative splicing of angiogenesis-related genes and their role in HIV-related cancers

    Directory of Open Access Journals (Sweden)

    Mthembu NN

    2017-03-01

    Full Text Available Nonkululeko N Mthembu,1 Zukile Mbita,2 Rodney Hull,1 Zodwa Dlamini1 1Research, Innovation and Engagements, Mangosuthu University of Technology, Durban, 2Department of Biochemistry, Microbiology and Biotechnology, University of Limpopo, Sovenga, South Africa Abstract: Alternative splicing of mRNA leads to an increase in proteome biodiversity by allowing the generation of multiple mRNAs, coding for multiple protein isoforms of various structural and functional properties from a single primary pre-mRNA transcript. The protein isoforms produced are tightly regulated in normal development but are mostly deregulated in various cancers. In HIV-infected individuals with AIDS, there is an increase in aberrant alternative splicing, resulting in an increase in HIV/AIDS-related cancers, such as Kaposi’s sarcoma, non-Hodgkin’s lymphoma, and cervical cancer. This aberrant splicing leads to abnormal production of protein and is caused by mutations in cis-acting elements or trans-acting factors in angiogenesis-related genes. Restoring the normal regulation of alternative splicing of angiogenic genes would alter the expression of protein isoforms and may confer normal cell physiology in patients with these cancers. This review highlights the abnormalities in alternative splicing of angiogenesis-related genes and their implication in HIV/AIDS-related cancers. This allows us to gain an insight into the pathogenesis of HIV/AIDS-related cancer and in turn elucidate the therapeutic potential of alternatively spliced genes in HIV/AIDS-related malignancies. Keywords: vascular endothelial growth factor, oncogenic viruses, hypoxia induced factor 1, Kaposi’s sarcoma, non-Hodgkin’s lymphoma, therapies targeting alternative splicing

  3. Selection BIAS: Stereotypes and discrimination related to having a history of cancer.

    Science.gov (United States)

    Martinez, Larry R; White, Craig D; Shapiro, Jenessa R; Hebl, Michelle R

    2016-01-01

    Although great strides have been made in increasing equality and inclusion in organizations, a number of stigmatized groups are overlooked by diversity initiatives, including people with a history of cancer. To examine the workplace experiences of these individuals in selection contexts, we conducted 3 complementary studies that assess the extent to which cancer is disclosed, the stereotypes associated with cancer in the workplace, and discrimination resulting from these stereotypes. In a pilot study, we surveyed 196 individuals with a history of cancer (across 2 samples) about their workplace disclosure habits. In Study 1, we explored stereotypes related to employees with a history of cancer using the framework outlined by the stereotype content model. In Study 2, we used a field study to assess the experiences of job applicants who indicated they were "cancer survivors" (vs. not) with both formal and interpersonal forms of discrimination. This research shows that cancer is disclosed at relatively high rates (pilot study), those with a history of cancer are stereotyped as being higher in warmth than competence (Study 1), and the stereotypes associated with those who have had cancer result in actual discrimination toward them (Study 2). We discuss the theory behind these findings and aim to inform both science and practice with respect to this growing workplace population. (c) 2016 APA, all rights reserved).

  4. Health-related quality of life outcome for oral cancer survivors after surgery and postoperative radiotherapy

    International Nuclear Information System (INIS)

    Fang, Fu-Min; Chien, Chih-Yen; Wang, Chong-Jong; Tsai, Wen-Ling; Chiu, Herng-Chia

    2004-01-01

    Health-related quality of life (HRQL) data are becoming an important supplement to information pertaining to treatment outcome for cancer patients. The purpose of this study was to evaluate the HRQL outcome for oral cancer survivors after surgery plus postoperative radiotherapy (RT) and to investigate the variables associated with their HRQL. Sixty-six oral cancer patients with cancer-free survival after surgery plus postoperative RT of >2 years were enrolled. The Short Form-36 (SF-36) questionnaire in the Taiwan Chinese version was self-reported by all participants at the clinics. The linear regression model was used to analyze the socio-demographic and medical-related variables correlated with the physical component summary (PCS) and mental component summary (MCS) in SF-36. The mean scores of the eight functional domains in the SF-36 were markedly lower for oral cancer survivors compared with the Taiwanese and US norms. Those with older age, lower annual family income, more advanced cancer stage and flap reconstruction had significantly worse PCS, and those with lower annual family income, unemployment and more advanced cancer stage reported significantly worse MCS. This model accounts for 63% of variance in PCS, and 51% in MCS. These results provided patient-reported evidence that oral cancer survivors lived with a worse HRQL compared with the general Taiwanese population. Socio-economic factors and cancer stage were important factors correlated with their HRQL. (authors)

  5. Vehicular Traffic-Related Polycyclic Aromatic Hydrocarbon Exposure and Breast Cancer Incidence: The Long Island Breast Cancer Study Project (LIBCSP).

    Science.gov (United States)

    Mordukhovich, Irina; Beyea, Jan; Herring, Amy H; Hatch, Maureen; Stellman, Steven D; Teitelbaum, Susan L; Richardson, David B; Millikan, Robert C; Engel, Lawrence S; Shantakumar, Sumitra; Steck, Susan E; Neugut, Alfred I; Rossner, Pavel; Santella, Regina M; Gammon, Marilie D

    2016-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure. Our study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence. Residential histories of 1,508 participants with breast cancer (case participants) and 1,556 particpants with no breast cancer (control participants) were assessed in a population-based investigation conducted in 1996-1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960-1995 were reconstructed using a model previously shown to generate estimates consistent with measured soil PAHs, PAH-DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression. The odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960-1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake [1.46 (0.89, 2.40)], but not among those with high fruit/vegetable intake [0.92 (0.53, 1.60)]. Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic-breast cancer association was higher for those with estrogen/progesterone-negative tumors [1.67 (0.91, 3.05) relative to control participants], but lower among all other tumor subtypes [0.80 (0.50, 1.27) compared with control participants]. In our population-based study, we observed positive associations between vehicular traffic-related

  6. Chronic Fatigue Syndrome (CFS) and Cancer Related Fatigue (CRF): two "fatigue" syndromes with overlapping symptoms and possibly related aetiologies.

    Science.gov (United States)

    Rovigatti, Ugo

    2012-12-01

    In July 2010, at the Muscle Fatigue Meeting, I presented an overview of Chronic Fatigue Syndrome and Cancer Related Fatigue, emphasizing a critical interpretation of the potential association between Chronic Fatigue Syndrome and Cancer Related Fatigue and a newly discovered retrovirus: Xenotropic Murine Related Virus. Since this association was hotly debated at that time, I suggested at the Meeting that it was wrong and most likely due to the identification of the wrong virus culprit. Today, 20 months after the Meeting, the first part of our prediction has turned out to be correct, as Xenotropic Murine Related Virus was shown to be a laboratory-created artefact. Still, the potential association of fatigue-syndromes with an infection (most likely viral) is sustained by a plethora of evidence and this overview will initially summarize data suggesting prior viral infection(s). The principal hypothesized mechanisms for both peripheral and central Chronic Fatigue Syndrome/Cancer Related Fatigue will be then summarized, also indicating plausible associations and triggering factors. All evidence accrued so far suggests that further research work should be performed in this interesting area and in order to identify an infectious agent for Chronic Fatigue Syndrome/Cancer Related Fatigue. One candidate RNA virus, Micro-Foci inducing Virus, will be described in this overview. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Toward stable genetic engineering of human o-glycosylation in plants

    DEFF Research Database (Denmark)

    Yang, Zhang; Bennett, Eric Paul; Jørgensen, Bodil

    2012-01-01

    Glycosylation is the most abundant and complex posttranslational modification to be considered for recombinant production of therapeutic proteins. Mucin-type (N-acetylgalactosamine [GalNAc]-type) O-glycosylation is found in eumetazoan cells but absent in plants and yeast, making these cell types...... an obvious choice for de novo engineering of this O-glycosylation pathway. We previously showed that transient implementation of O-glycosylation capacity in plants requires introduction of the synthesis of the donor substrate UDP-GalNAc and one or more polypeptide GalNAc-transferases for incorporating Gal......NAc residues into proteins. Here, we have stably engineered O-glycosylation capacity in two plant cell systems, soil-grown Arabidopsis (Arabidopsis thaliana) and tobacco (Nicotiana tabacum) Bright Yellow-2 suspension culture cells. Efficient GalNAc O-glycosylation of two stably coexpressed substrate O...

  8. The node-weighted Steiner tree approach to identify elements of cancer-related signaling pathways.

    Science.gov (United States)

    Sun, Yahui; Ma, Chenkai; Halgamuge, Saman

    2017-12-28

    Cancer constitutes a momentous health burden in our society. Critical information on cancer may be hidden in its signaling pathways. However, even though a large amount of money has been spent on cancer research, some critical information on cancer-related signaling pathways still remains elusive. Hence, new works towards a complete understanding of cancer-related signaling pathways will greatly benefit the prevention, diagnosis, and treatment of cancer. We propose the node-weighted Steiner tree approach to identify important elements of cancer-related signaling pathways at the level of proteins. This new approach has advantages over previous approaches since it is fast in processing large protein-protein interaction networks. We apply this new approach to identify important elements of two well-known cancer-related signaling pathways: PI3K/Akt and MAPK. First, we generate a node-weighted protein-protein interaction network using protein and signaling pathway data. Second, we modify and use two preprocessing techniques and a state-of-the-art Steiner tree algorithm to identify a subnetwork in the generated network. Third, we propose two new metrics to select important elements from this subnetwork. On a commonly used personal computer, this new approach takes less than 2 s to identify the important elements of PI3K/Akt and MAPK signaling pathways in a large node-weighted protein-protein interaction network with 16,843 vertices and 1,736,922 edges. We further analyze and demonstrate the significance of these identified elements to cancer signal transduction by exploring previously reported experimental evidences. Our node-weighted Steiner tree approach is shown to be both fast and effective to identify important elements of cancer-related signaling pathways. Furthermore, it may provide new perspectives into the identification of signaling pathways for other human diseases.

  9. Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S)

    DEFF Research Database (Denmark)

    O'Sullivan, Brian; Huang, Shao Hui; Su, Jie

    2016-01-01

    BACKGROUND: Human papillomavirus-related (HPV+) oropharyngeal cancer is a rapidly emerging disease with generally good prognosis. Many prognostic algorithms for oropharyngeal cancer incorporate HPV status as a stratification factor, rather than recognising the uniqueness of HPV+ disease. The Inte...

  10. Asbestos-related occupational cancers compensated under the Spanish National Insurance System, 1978-2011.

    Science.gov (United States)

    García-Gómez, Montserrat; Menéndez-Navarro, Alfredo; López, Rosario Castañeda

    2015-01-01

    In 1978, asbestos-related occupational cancers were added to the Spanish list of occupational diseases. However, there are no full accounts of compensated cases since their inclusion. To analyze the cases of asbestos-related cancer recognized as occupational in Spain between 1978 and 2011. Cases were obtained from the Spanish Employment Ministry. Specific incidence rates by year, economic activity, and occupation were obtained. We compared mortality rates of mesothelioma and bronchus and lung cancer mortality in Spain and the European Union. Between 1978 and 2011, 164 asbestos-related occupational cancers were recognized in Spain, with a mean annual rate of 0·08 per 10(5) employees (0·13 in males, 0·002 in females). Under-recognition rates were an estimated 93·6% (males) and 99·7% (females) for pleural mesothelioma and 98·8% (males) and 100% (females) for bronchus and lung cancer. In Europe for the year 2000, asbestos-related occupational cancer rates ranged from 0·04 per 10(5) employees in Spain to 7·32 per 10(5) employees in Norway. These findings provide evidence of gross under-recognition of asbestos-related occupational cancers in Spain. Future work should investigate cases treated in the National Healthcare System to better establish the impact of asbestos on health in Spain.

  11. Optimizing prognosis-related key miRNA-target interactions responsible for cancer metastasis.

    Science.gov (United States)

    Zhao, Hongying; Yuan, Huating; Hu, Jing; Xu, Chaohan; Liao, Gaoming; Yin, Wenkang; Xu, Liwen; Wang, Li; Zhang, Xinxin; Shi, Aiai; Li, Jing; Xiao, Yun

    2017-12-12

    Increasing evidence suggests that the abnormality of microRNAs (miRNAs) and their downstream targets is frequently implicated in the pathogenesis of human cancers, however, the clinical benefit of causal miRNA-target interactions has been seldom studied. Here, we proposed a computational method to optimize prognosis-related key miRNA-target interactions by combining transcriptome and clinical data from thousands of TCGA tumors across 16 cancer types. We obtained a total of 1,956 prognosis-related key miRNA-target interactions between 112 miRNAs and 1,443 their targets. Interestingly, these key target genes are specifically involved in tumor progression-related functions, such as 'cell adhesion' and 'cell migration'. Furthermore, they are most significantly correlated with 'tissue invasion and metastasis', a hallmark of metastasis, in ten distinct types of cancer through the hallmark analysis. These results implicated that the prognosis-related key miRNA-target interactions were highly associated with cancer metastasis. Finally, we observed that the combination of these key miRNA-target interactions allowed to distinguish patients with good prognosis from those with poor prognosis both in most TCGA cancer types and independent validation sets, highlighting their roles in cancer metastasis. We provided a user-friendly database named miRNATarget (freely available at http://biocc.hrbmu.edu.cn/miRNATar/), which provides an overview of the prognosis-related key miRNA-target interactions across 16 cancer types.

  12. Effect of physical therapy on breast cancer related lymphedema

    DEFF Research Database (Denmark)

    Tambour, Mette; Tange, Berit; Christensen, Robin Daniel Kjersgaard

    2014-01-01

    BACKGROUND: Physical therapy treatment of patients with lymphedema includes treatment based on the principles of 'Complete Decongestive Therapy' (CDT). CDT consists of the following components; skin care, manual lymphatic drainage, bandaging and exercises. The scientific evidence regarding what...... trial. A total of 160 breast cancer patients with arm lymphedema will be recruited from 3 hospitals and randomized into one of two treatment groups A: Complete Decongestive Therapy including manual drainage or B: Complete Decongestive Therapy without manual lymphatic drainage. The intervention period...... type of treatment is most effective is sparse. The objective of this study is to investigate whether CDT is equally effective if it includes manual lymphatic drainage or not in the treatment of arm lymphedema among patients with breast cancer. METHODS/DESIGN: A randomized, single-blind, equivalence...

  13. ESPEN expert group recommendations for action against cancer-related malnutrition.

    Science.gov (United States)

    Arends, J; Baracos, V; Bertz, H; Bozzetti, F; Calder, P C; Deutz, N E P; Erickson, N; Laviano, A; Lisanti, M P; Lobo, D N; McMillan, D C; Muscaritoli, M; Ockenga, J; Pirlich, M; Strasser, F; de van der Schueren, M; Van Gossum, A; Vaupel, P; Weimann, A

    2017-10-01

    Patients with cancer are at particularly high risk for malnutrition because both the disease and its treatments threaten their nutritional status. Yet cancer-related nutritional risk is sometimes overlooked or under-treated by clinicians, patients, and their families. The European Society for Clinical Nutrition and Metabolism (ESPEN) recently published evidence-based guidelines for nutritional care in patients with cancer. In further support of these guidelines, an ESPEN oncology expert group met for a Cancer and Nutrition Workshop in Berlin on October 24 and 25, 2016. The group examined the causes and consequences of cancer-related malnutrition, reviewed treatment approaches currently available, and built the rationale and impetus for clinicians involved with care of patients with cancer to take actions that facilitate nutrition support in practice. The content of this position paper is based on presentations and discussions at the Berlin meeting. The expert group emphasized 3 key steps to update nutritional care for people with cancer: (1) screen all patients with cancer for nutritional risk early in the course of their care, regardless of body mass index and weight history; (2) expand nutrition-related assessment practices to include measures of anorexia, body composition, inflammatory biomarkers, resting energy expenditure, and physical function; (3) use multimodal nutritional interventions with individualized plans, including care focused on increasing nutritional intake, lessening inflammation and hypermetabolic stress, and increasing physical activity. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  14. Cancer-related fatigue and depression in breast cancer patients postchemotherapy: Different associations with optimism and stress appraisals.

    Science.gov (United States)

    Levkovich, Inbar; Cohen, Miri; Pollack, Shimon; Drumea, Karen; Fried, Georgeta

    2015-10-01

    Symptoms of depression and cancer-related fatigue (CRF) are common among breast cancer patients postchemotherapy and may seriously impair quality of life (QoL). This study aimed to assess the relationship between depression and CRF in breast cancer patients postchemotherapy and to examine their relationships to optimism and to threat and challenge appraisals. Participants included 95 breast cancer patients (stages 1-3) 1 to 6 months after completion of chemotherapy. Patients submitted personal and medical details and completed the following: physical symptom questionnaires (EORTC QLQ-C30, and QLQ-BR23), a symptoms of depression questionnaire (CES-D), the Fatigue Symptom Inventory (FSI), the Life Orientation Test (LOT-R), and a stress appraisals questionnaire. We found levels of depression, CRF, and appraisals of cancer as a threat to bemoderate and levels of optimism and appraisals of cancer as a challenge to be high. Depression and CRF were positively associated. A multivariate regression analysis revealed that 51% of the CRF variancewas explained; physical symptoms and threat appraisal were significantly associated with CRF. A 67% of the CRF variance of depression was explained; challenge and threat appraisals were significantly associated with depression [corrected]. Although CRF and depression were often experienced simultaneously and both were found to be higher among individuals who gave higher appraisals of cancer as a threat, only depression was related to optimism and challenge appraisals, while CRF was related mainly to intensity of physical symptoms. The different pattern of associations between optimism and appraisals warrants further clinical attention as well as future study.

  15. Immunoglobulin G (IgG) Fab glycosylation analysis using a new mass spectrometric high-throughput profiling method reveals pregnancy-associated changes.

    Science.gov (United States)

    Bondt, Albert; Rombouts, Yoann; Selman, Maurice H J; Hensbergen, Paul J; Reiding, Karli R; Hazes, Johanna M W; Dolhain, Radboud J E M; Wuhrer, Manfred

    2014-11-01

    The N-linked glycosylation of the constant fragment (Fc) of immunoglobulin G has been shown to change during pathological and physiological events and to strongly influence antibody inflammatory properties. In contrast, little is known about Fab-linked N-glycosylation, carried by ∼ 20% of IgG. Here we present a high-throughput workflow to analyze Fab and Fc glycosylation of polyclonal IgG purified from 5 μl of serum. We were able to detect and quantify 37 different N-glycans by means of MALDI-TOF-MS analysis in reflectron positive mode using a novel linkage-specific derivatization of sialic acid. This method was applied to 174 samples of a pregnancy cohort to reveal Fab glycosylation features and their change with pregnancy. Data analysis revealed marked differences between Fab and Fc glycosylation, especially in the levels of galactosylation and sialylation, incidence of bisecting GlcNAc, and presence of high mannose structures, which were all higher in the Fab portion than the Fc, whereas Fc showed higher levels of fucosylation. Additionally, we observed several changes during pregnancy and after delivery. Fab N-glycan sialylation was increased and bisection was decreased relative to postpartum time points, and nearly complete galactosylation of Fab glycans was observed throughout. Fc glycosylation changes were similar to results described before, with increased galactosylation and sialylation and decreased bisection during pregnancy. We expect that the parallel analysis of IgG Fab and Fc, as set up in this paper, will be important for unraveling roles of these glycans in (auto)immunity, which may be mediated via recognition by human lectins or modulation of antigen binding. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Immunoglobulin G (IgG) Fab Glycosylation Analysis Using a New Mass Spectrometric High-throughput Profiling Method Reveals Pregnancy-associated Changes*

    Science.gov (United States)

    Bondt, Albert; Rombouts, Yoann; Selman, Maurice H. J.; Hensbergen, Paul J.; Reiding, Karli R.; Hazes, Johanna M. W.; Dolhain, Radboud J. E. M.; Wuhrer, Manfred

    2014-01-01

    The N-linked glycosylation of the constant fragment (Fc) of immunoglobulin G has been shown to change during pathological and physiological events and to strongly influence antibody inflammatory properties. In contrast, little is known about Fab-linked N-glycosylation, carried by ∼20% of IgG. Here we present a high-throughput workflow to analyze Fab and Fc glycosylation of polyclonal IgG purified from 5 μl of serum. We were able to detect and quantify 37 different N-glycans by means of MALDI-TOF-MS analysis in reflectron positive mode using a novel linkage-specific derivatization of sialic acid. This method was applied to 174 samples of a pregnancy cohort to reveal Fab glycosylation features and their change with pregnancy. Data analysis revealed marked differences between Fab and Fc glycosylation, especially in the levels of galactosylation and sialylation, incidence of bisecting GlcNAc, and presence of high mannose structures, which were all higher in the Fab portion than the Fc, whereas Fc showed higher levels of fucosylation. Additionally, we observed several changes during pregnancy and after delivery. Fab N-glycan sialylation was increased and bisection was decreased relative to postpartum time points, and nearly complete galactosylation of Fab glycans was observed throughout. Fc glycosylation changes were similar to results described before, with increased galactosylation and sialylation and decreased bisection during pregnancy. We expect that the parallel analysis of IgG Fab and Fc, as set up in this paper, will be important for unraveling roles of these glycans in (auto)immunity, which may be mediated via recognition by human lectins or modulation of antigen binding. PMID:25004930

  17. Efficacy and Safety of Two Methadone Titration Methods for the Treatment of Cancer-Related Pain: The EQUIMETH2 Trial (Methadone for Cancer-Related Pain).

    Science.gov (United States)

    Poulain, Philippe; Berleur, Marie-Pierre; Lefki, Shimsi; Lefebvre, Danièle; Chvetzoff, Gisèle; Serra, Eric; Tremellat, Fibra; Derniaux, Alain; Filbet, Marilène

    2016-11-01

    In the European Association for Palliative Care recommendations for cancer pain management, there was no consensus regarding the indications, titration, or monitoring of methadone. This national, randomized, multicenter trial aimed to compare two methadone titration methods (stop-and-go vs. progressive) in patients with cancer-related pain who were inadequately relieved by or intolerant to Level 3 opioids. The primary end point was the rate of success/failure at Day 4, defined as pain relief (reduction of at least two points on the visual scale and a pain score methods were considered equally easy to perform by nearly 60% of the clinicians. Methadone is an effective and sustainable second-line alternative opioid for the treatment of cancer-related pain. The methods of titration are comparable in terms of efficacy, safety, and ease of use. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

  18. Surveillance Imaging in HPV-related Oropharyngeal Cancer.

    Science.gov (United States)

    Su, William; Miles, Brett A; Posner, Marshall; Som, Peter; Kostakoglu, Lale; Gupta, Vishal; Bakst, Richard L

    2018-03-01

    Current guidelines derived from a pre-human papilloma virus (HPV) era in oropharyngeal cancer do not recommend routine surveillance imaging. We aimed to analyze the method of recurrence detection in HPV+ disease to determine a role for follow-up imaging. All HPV+ and HPV- oropharyngeal cancer patients treated at our institution from 2005-2016 with biopsy-proven recurrence were identified and their method of recurrence detection was analyzed. A total of 16 HPV+ oropharyngeal cancer patients were identified to have recurrence, 12 (75%) of which experienced distant recurrence and 13 (81.3%) were detected asymptomatically with imaging at a median time of 19.7 months after initial treatment and verifying no residual disease. Twelve (75%) detections were with PET-CT. While HPV- patients (17 patients) also have a high rate of asymptomatic detection (16 patients, 94.1%), their 3-year post-recurrence survival was significantly lower at 6.5% compared to 83.6% for the HPV+ group (pHPV+ patients, a large proportion of failures are asymptomatic distant metastases, which occur beyond 6 months following treatment completion, and are detected with whole body imaging alone. In light of long term post-recurrence survival observed, this preliminary data suggests that routine surveillance imaging should be further studied for HPV+ disease. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. Scoring of treatment-related late effects in prostate cancer

    International Nuclear Information System (INIS)

    Livsey, Jacqueline E.; Routledge, Jacqueline; Burns, Meriel; Swindell, Rick; Davidson, Susan E.; Cowan, Richard A.; Logue, John P.; Wylie, James P.

    2002-01-01

    Background and purpose: To assess the correlation between different general and organ specific quality of life and morbidity scoring methods in a cohort of men treated with radical radiotherapy for prostate cancer. Materials and methods: Men who had been treated with radical radiotherapy (50 Gy in 16 fractions over 21 days) for localized prostate cancer more than 3 years previously and who had no evidence of recurrent disease were invited to take part in the study. A total of 101 of 135 invited patients agreed and completed LENT/SOMA, UCLA Prostate Cancer Index, and 36 item RAND Health survey questionnaires. Results: The patients had comparable results with other published series with respect to the UCLA and SF-36 indices. There was significant correlation between the corresponding parts of the UCLA and LENT/SOMA scales (P<0.0005). However, for the same symptoms, a patient tended to score lower (worse) on the UCLA scale in comparison to LENT/SOMA. The relationship between the average LENT/SOMA score and maximum score was also not straightforward with each set of data revealing different information. Conclusions: The LENT/SOMA questions were, in the main, more wide-ranging and informative than the UCLA index. It is helpful to give both the overall and maximum LENT/SOMA scores to most efficiently use all of the data. There may need to be a further LENT/SOMA question to allow both symptoms of tenesmus and faecal urgency to be fully addressed

  20. Bioinformatics analysis of breast cancer bone metastasis related gene-CXCR4

    Institute of Scientific and Technical Information of China (English)

    Heng-Wei Zhang; Xian-Fu Sun; Ya-Ning He; Jun-Tao Li; Xu-Hui Guo; Hui Liu

    2013-01-01

    Objective: To analyze breast cancer bone metastasis related gene-CXCR4. Methods: This research screened breast cancer bone metastasis related genes by high-flux gene chip. Results:It was found that the expressions of 396 genes were different including 165 up-regulations and 231 down-regulations. The expression of chemokine receptor CXCR4 was obviously up-regulated in the tissue with breast cancer bone metastasis. Compared with the tissue without bone metastasis, there was significant difference, which indicated that CXCR4 played a vital role in breast cancer bone metastasis. Conclusions: The bioinformatics analysis of CXCR4 can provide a certain basis for the occurrence and diagnosis of breast cancer bone metastasis, target gene therapy and evaluation of prognosis.

  1. Relation of occupations to the regional differences of lung cancer motality in Fukuoka Prefecture.

    Science.gov (United States)

    Shigematsu, T; Yamasaki, M

    1977-07-01

    Geographic pattern of lung cancer mortality in Fukuoka Prefecture showed elevated mortalities among males in the Chikuho district where many coal-mines had long been operated as one of the biggest coal-mining areas in Japan. The analysis in relations of occupations to lung cancer mortality revealed that consistently significant correlations exist between lung cancer mortality, and mining and quarrying occupations in every census year after World War II. No other occupations showed consistent relations to lung cancer though a few significant correlations were found only in the recent years. The results appear to suggest that elevated risk of lung cancer among coal-mining workers may exist and deserve further analytical study.

  2. Genetic variants in hormone-related genes and risk of breast cancer.

    Directory of Open Access Journals (Sweden)

    Tess Clendenen

    Full Text Available Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent. We conducted a case-control study nested within two prospective cohorts to assess the relationship between specific genetic variants in hormone-related genes and breast cancer risk. In total, 1164 cases and 2111 individually-matched controls were included in the study. We did not observe an association between potential functional genetic polymorphisms in the estrogen pathway, SHBG rs6259, ESR1 rs2234693, CYP19 rs10046 and rs4775936, and UGT1A1 rs8175347, or the progesterone pathway, PGR rs1042838, with the risk of breast cancer. Our results suggest that these genetic variants do not have a strong effect on breast cancer risk.

  3. A Novel Strategy for Characterization of Glycosylated Proteins Separated by Gel Electrophoresis

    DEFF Research Database (Denmark)

    Larsen, Martin; Skottrup, Peter; Enghild, Jan Johannes

    Protein glycosylation can be vital for changing the function or physiochemical properties of a protein. Abnormal glycosylation can lead to protein malfunction, resulting in severe diseases. Therefore, it is important to develop techniques for characterization of such modifications in proteins...... graphite powder micro-columns in combination with mass spectrometry. The method is faster and more sensitive than previous approaches and would be ideal for proteomics studies and verification of correct glycosylation of recombinant glycoproteins....

  4. Pre-diagnosis employment status and financial circumstances predict cancer-related financial stress and strain among breast and prostate cancer survivors.

    Science.gov (United States)

    Sharp, Linda; Timmons, Aileen

    2016-02-01

    Cancer may have a significant financial impact on patients, but the characteristics that predispose patients to cancer-related financial hardship are poorly understood. We investigated factors associated with cancer-related financial stress and strain in breast and prostate cancer survivors in Ireland, which has a complex mixed public-private healthcare system. Postal questionnaires were distributed to 1373 people diagnosed with cancer 3-24 months previously identified from the National Cancer Registry Ireland. Outcomes were cancer-related financial stress (impact of cancer diagnosis on household ability to make ends meet) and financial strain (concerns about household financial situation since cancer diagnosis). Modified Poisson regression was used to estimate relative risks (RR) for factors associated with cancer-related financial stress and strain. Seven hundred forty survivors participated (response rate = 54 %). Of the respondents, 48 % reported cancer-related financial stress and 32 % cancer-related financial strain. Compared to those employed at diagnosis, risk of cancer-related financial stress was significantly lower in those not working (RR = 0.71, 95 % CI 0.58-0.86) or retired (RR = 0.48, 95 % CI 0.34-0.68). It was significantly higher in those who had dependents; experienced financial stress pre-diagnosis; had a mortgage/personal loans; had higher direct medical out-of-pocket costs; and had increased household bills post-diagnosis. For cancer-related financial strain, significant associations were found with dependents, pre-diagnosis employment status and pre-diagnosis financial stress; risk was lower in those with higher direct medical out-of-pocket costs. Cancer-related financial stress and strain are common. Pre-diagnosis employment status and financial circumstances are important predictors of post-diagnosis financial wellbeing. These findings could inform development of tools to identify patients/survivors most in need of financial

  5. Neoadjuvant twice daily chemoradiotherapy for esophageal cancer: Treatment-related mortality and long-term outcomes

    Directory of Open Access Journals (Sweden)

    Stuart E. Samuels, MD, PhD

    2017-07-01

    Conclusion: Neoadjuvant twice-daily chemoradiation for esophageal cancer is a safe and effective alternative to daily fractionation with low treatment-related mortality and long-term outcomes similar to standard fractionation courses.

  6. Cancer-Related Post-traumatic Stress (PDQ®)—Health Professional Version

    Science.gov (United States)

    Cancer-related post-traumatic stress (PTS) can occur any time from diagnosis until the end of treatment; treatment used in PTSD can be useful in reducing distress. Get comprehensive information on PTS in this summary for clinicians.

  7. Vasopressin Gene-Related Products in the Management of Breast Cancer

    National Research Council Canada - National Science Library

    North, William

    1999-01-01

    ...), and this information coupled with an absence of vasopressin gene-related products from fibrocystic disease potentially provides us with a new screening test for distinguishing both breast cancer...

  8. Vasopressin Gene-Related Products in the Management of Breast Cancer

    National Research Council Canada - National Science Library

    North, William

    1998-01-01

    .... The VP gene is expressed by seemingly all breast cancers and by all DCIS, and this information coupled with an absence of VP gene-related products from fibrocystic disease potentially provides us...

  9. Topic Modeling of Smoking- and Cessation-Related Posts to the American Cancer Society's Cancer Survivor Network (CSN): Implications for Cessation Treatment for Cancer Survivors Who Smoke.

    Science.gov (United States)

    Westmaas, J Lee; McDonald, Bennett R; Portier, Kenneth M

    2017-08-01

    Smoking is a risk factor in at least 18 cancers, and approximately two-thirds of cancer survivors continue smoking following diagnosis. Text mining of survivors' online posts related to smoking and quitting could inform strategies to reduce smoking in this vulnerable population. We identified posts containing smoking/cessation-related keywords from the Cancer Survivors Network (CSN), an online cancer survivor community of 166 000 members and over 468 000 posts since inception. Unsupervised topic model analysis of posts since 2000 using Latent Dirichlet Allocation extracted 70 latent topics which two subject experts inspected for themes based on representative terms. Posterior analysis assessed the distribution of topics within posts, and the range of themes discussed across posts. Less than 1% of posts (n = 3998) contained smoking/cessation-related terms, and covered topics related to cancer diagnoses, treatments, and coping. The most frequent smoking-related topics were quit smoking methods (5.4% of posts), and the environment for quitters (2.9% of posts), such as the stigma associated with being a smoker diagnosed with cancer and lack of empathy experienced compared to nonsmokers. Smoking as a risk factor for one's diagnosis was a primary topic in only 1.7% of smoking/cessation-related posts. The low frequency of smoking/cessation-related posts may be due to expected criticism/stigma for smoking but may also suggests a need for health care providers to address smoking and assist with quitting in the diagnostic and treatment process. Topic model analysis revealed potential barriers that should be addressed in devising clinical or population-level interventions for cancer survivors who smoke. Although smoking is a major risk factor for cancer, little is known about cancer patients' or survivors' views or concerns about smoking and quitting. This study used text mining of posts to an online community of cancer patients and survivors to investigate contexts in which

  10. Relationship between cancer-related traumatic stress and family milestone achievement in adolescent and young adult survivors of childhood cancer.

    Science.gov (United States)

    Tillery, Rachel; Beal, Sarah J; Thompson, Aimee N; Pai, Ahna L H

    2018-06-01

    Late physical and emotional effects of cancer treatment pose a burden for adolescent and young adult survivors of childhood cancer, including family milestone achievement. This brief report examined links between ongoing cancer-related post-traumatic stress symptoms (CR-PTSS) and family milestone achievement. Survivors (n = 51; M age  = 24.73, SD = 8.20) completed CR-PTSS and family formation questionnaires. Descriptive statistics, univariate parameter-constraints, and correlation analyses examined relations among study variables. Ongoing intrusive thoughts and hyperarousal were negatively linked to family identity development and family achievement. Findings from the present study provide support that ongoing CR-PTSS may be a barrier to family formation. © 2018 Wiley Periodicals, Inc.

  11. Nutritional status and related factors of patients with advanced gastrointestinal cancer.

    Science.gov (United States)

    Zhang, Liyan; Lu, Yuhan; Fang, Yu

    2014-04-14

    The scored Patient-Generated Subjective Global Assessment (PG-SGA) is considered to be the most appropriate tool for detecting malnutrition in cancer patients. In particular, malignant tumours derived from the gastrointestinal tract may impair nutrient intake and absorption and cause malnutrition. We carried out a cross-sectional study to assess the nutritional status and related factors of patients with gastrointestinal cancer. Nutritional status was determined using the scored PG-SGA in patients (n 498) with advanced gastrointestinal cancer admitted to the Gastrointestinal Medical Oncology Unit at Beijing Cancer Hospital between 1 August 2012 and 28 February 2013. The possible related factors including age, sex, hospitalisation frequency and pathology were explored. We found that 98% of the patients required nutrition intervention and 54% of the patients required improved nutrition-related symptom management and/or urgent nutritional support (PG-SGA score ≥9). Factors related to malnutrition were age (r 0.103, Pcancer had a lower risk of malnutrition than patients with other types of gastrointestinal cancer (F=35.895, Pnutritional status of gastrointestinal patients, especially those at a higher risk of malnutrition, such as elderly patients, those hospitalised for the first time, male patients and those with other types of gastrointestinal cancer except rectal cancer. The nutritional status of these patients should be evaluated and they should be given proper nutrition education and nutritional support in a timely manner.

  12. Mutations altering the gammaretrovirus endoproteolytic motif affect glycosylation of the envelope glycoprotein and early events of the virus life cycle

    Energy Technology Data Exchange (ETDEWEB)

    Argaw, Takele; Wilson, Carolyn A., E-mail: carolyn.wilson@fda.hhs.gov

    2015-01-15

    Previously, we found that mutation of glutamine to proline in the endoproteolytic cleavage signal of the PERV-C envelope (RQKK to RPKK) resulted in non-infectious vectors. Here, we show that RPKK results in a non-infectious vector when placed in not only a PERV envelope, but also the envelope of a related gammaretrovirus, FeLV-B. The amino acid substitutions do not prevent envelope precursor cleavage, viral core and genome assembly, or receptor binding. Rather, the mutations result in the formation of hyperglycosylated glycoprotein and a reduction in the reverse transcribed minus strand synthesis and undetectable 2-LTR circular DNA in cells exposed to vectors with these mutated envelopes. Our findings suggest novel functions associated with the cleavage signal sequence that may affect trafficking through the glycosylation machinery of the cell. Further, the glycosylation status of the envelope appears to impact post-binding events of the viral life cycle, either membrane fusion, internalization, or reverse transcription. - Highlights: • Env cleavage signal impacts infectivity of gammaretroviruses. • Non-infectious mutants have hyper-glycosylated envelope that bind target cells. • Non-infectious mutants have defects in the formation of the double-stranded DNA. • Env cleavage motif has functions beyond cleavage of the env precursor.

  13. Causes of Cancer Death Among First-Degree Relatives in Japanese Families with Lynch Syndrome.

    Science.gov (United States)

    Tanakaya, Kohji; Yamaguchi, Tatsuro; Ishikawa, Hideki; Hinoi, Takao; Furukawa, Yoichi; Hirata, Keiji; Saida, Yoshihisa; Shimokawa, Mototsugu; Arai, Masami; Matsubara, Nagahide; Tomita, Naohiro; Tamura, Kazuo; Sugano, Kokichi; Ishioka, Chikashi; Yoshida, Teruhiko; Ishida, Hideyuki; Watanabe, Toshiaki; Sugihara, Kenichi

    2016-04-01

    To elucidate the causes of cancer death in Japanese families with Lynch syndrome (LS). The distributions of cancer deaths in 485 individuals from 67 families with LS (35, 30, and two families with MutL homologue 1 (MLH1), MSH2, and MSH6 gene mutations, respectively), obtained from the Registry of the Japanese Society for Cancer of the Colon and Rectum were analyzed. Among 98 cancer deaths of first-degree relatives of unknown mutation status, 53%, 19%, 13% (among females), 7% (among females) and 5% were due to colorectal, gastric, uterine, ovarian, and hepatobiliary cancer, respectively. The proportion of deaths from extra-colonic cancer was significantly higher in families with MSH2 mutation than in those with MLH1 mutation (p=0.003). In addition to colonic and uterine cancer, management and surveillance targeting gastric, ovarian and hepatobiliary cancer are considered important for Japanese families with LS. Extra-colonic cancer in families with MSH2 mutation might require for more intensive surveillance. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  14. Dietary-induced cancer prevention: An expanding research arena of emerging diet related to healthcare system.

    Science.gov (United States)

    Pal, Dilipkumar; Banerjee, Subham; Ghosh, Ashoke Kumar

    2012-01-01

    Diet plays a vital role in the management of cancer because they are the source of important physiologically functional components. Scientific observations support the idea that dietary supplement can prevent breast cancer recurrences. Strong correlations are established between the high intake of saturated fat and the incidence of different types of cancer. It is found that chronic alcohol consumption is associated with increased risk of cancers of oral cavity, pharynx, esophagus, and larynx. Again, some evidences are also found regarding phosphorous, glutamate level in the body, and incidence of cancer. Different physiologically functional components are found in the dietary materials. Fibers, the major dietary components, have long been recognized for the unique properties in the treatment of cancer, which are related to its antineoplastic functions. Antioxidant rich diet has been added to the list of cancer-preventing dietary components. Also, recently published research has shown that natural carotenoids in the diet leads to a normalization of body epithelial cells and protects against the risk of stomach and esophagus cancer, and improves the immune system's response. Again, fruit juices, processed vegetable juices, orange peel, green tea, vitamins, flavonoids, and trace materials have cancer inhibitory properties. Clearly, there has been increasing recognition of chemoprotective functions. Now, it can be recognized for another kind of functionality for the improvement of the health of mankind.

  15. Dietary-induced cancer prevention: An expanding research arena of emerging diet related to healthcare system

    Directory of Open Access Journals (Sweden)

    Dilipkumar Pal

    2012-01-01

    Full Text Available Diet plays a vital role in the management of cancer because they are the source of important physiologically functional components. Scientific observations support the idea that dietary supplement can prevent breast cancer recurrences. Strong correlations are established between the high intake of saturated fat and the incidence of different types of cancer. It is found that chronic alcohol consumption is associated with increased risk of cancers of oral cavity, pharynx, esophagus, and larynx. Again, some evidences are also found regarding phosphorous, glutamate level in the body, and incidence of cancer. Different physiologically functional components are found in the dietary materials. Fibers, the major dietary components, have long been recognized for the unique properties in the treatment of cancer, which are related to its antineoplastic functions. Antioxidant rich diet has been added to the list of cancer-preventing dietary components. Also, recently published research has shown that natural carotenoids in the diet leads to a normalization of body epithelial cells and protects against the risk of stomach and esophagus cancer, and improves the immune system′s response. Again, fruit juices, processed vegetable juices, orange peel, green tea, vitamins, flavonoids, and trace materials have cancer inhibitory properties. Clearly, there has been increasing recognition of chemoprotective functions. Now, it can be recognized for another kind of functionality for the improvement of the health of mankind.

  16. A Chinese Decoction, Kuan-Sin-Yin, Improves Autonomic Function and Cancer-Related Symptoms of Metastatic Colon Cancer.

    Science.gov (United States)

    Chien, Tsai-Ju; Liu, Chia-Yu; Ko, Pin-Hao; Hsu, Chung-Hua

    2016-03-01

    Kuan-Sin-Yin (KSY) is a traditional Chinese medicine (TCM) decoction, which has been shown to have cytostatic effects on cancer cells and involved in the TCM theory of promoting yin-yang balance.Sonce many cancer patients suffer from autonomic dysfunction (AD), which correspond to yin-yang imbalance in TCM. The aim of this study is to evaluate the possible effect of KSY in metastatic colon cancer (mCRC) patients with AD. We conducted a single-group experiment. Total 52 qualified patients were enrolled. Participants took the KSY daily for 2 weeks. The primary outcome was KSY efficacy as reflected in the heart rate variability (HRV) and electrical conductivity (µA) over 12 meridian points. Autonomic function was examined before and after the KSY intervention. The vagal and sympathetic tone were recorded by HRV; 12 meridian energies were measured using a meridian energy analysis device. Secondary outcomes were cancer-related symptoms and patient quality of life (QoL). The results showed that the KSY intervention improved AD via increasing the vagal tone (HF: P = .041), but not the sympathetic tone (LF: P = .154); total autonomic activity was significantly enhanced (HRV activity: P = .013). Intriguingly, energy increased more over the yin meridian (P = .010) than over the yang meridian (P = .015). Cancer-related symptoms and QoL were significantly improved (P yin-yang concept of energy. © The Author(s) 2015.

  17. Tumour biology of obesity-related cancers: understanding the molecular concept for better diagnosis and treatment.

    Science.gov (United States)

    Teoh, Seong Lin; Das, Srijit

    2016-11-01

    Obesity continues to be a major global problem. Various cancers are related to obesity and proper understanding of their aetiology, especially their molecular tumour biology is important for early diagnosis and better treatment. Genes play an important role in the development of obesity. Few genes such as leptin, leptin receptor encoded by the db (diabetes), pro-opiomelanocortin, AgRP and NPY and melanocortin-4 receptors and insulin-induced gene 2 were linked to obesity. MicroRNAs control gene expression via mRNA degradation and protein translation inhibition and influence cell differentiation, cell growth and cell death. Overexpression of miR-143 inhibits tumour growth by suppressing B cell lymphoma 2, extracellular signal-regulated kinase-5 activities and KRAS oncogene. Cancers of the breast, uterus, renal, thyroid and liver are also related to obesity. Any disturbance in the production of sex hormones and insulin, leads to distortion in the balance between cell proliferation, differentiation and apoptosis. The possible mechanism linking obesity to cancer involves alteration in the level of adipokines and sex hormones. These mediators act as biomarkers for cancer progression and act as targets for cancer therapy and prevention. Interestingly, many anti-cancerous drugs are also beneficial in treating obesity and vice versa. We also reviewed the possible link in the mechanism of few drugs which act both on cancer and obesity. The present review may be important for molecular biologists, oncologists and clinicians treating cancers and also pave the way for better therapeutic options.

  18. Readability analysis of online resources related to lung cancer.

    Science.gov (United States)

    Weiss, Kathleen D; Vargas, Christina R; Ho, Olivia A; Chuang, Danielle J; Weiss, Jonathan; Lee, Bernard T

    2016-11-01

    Patients seeking health information commonly use the Internet as the first source for material. Studies show that well-informed patients have increased involvement, satisfaction, and healthcare outcomes. As one-third of Americans have only basic or below basic health literacy, the National Institutes of Health and American Medical Association recommend patient-directed health resources be written at a sixth-grade reading level. This study evaluates the readability of commonly accessed online resources on lung cancer. A search for "lung cancer" was performed using Google and Bing, and the top 10 websites were identified. Location services were disabled, and sponsored sites were excluded. Relevant articles (n = 109) with patient-directed content available directly from the main sites were downloaded. Readability was assessed using 10 established methods and analyzed with articles grouped by parent website. The average reading grade level across all sites was 11.2, with a range from 8.8 (New Fog Count) to 12.2 (Simple Measure of Gobbledygook). The average Flesch Reading Ease score was 52, corresponding with fairly difficult to read text. The readability varied when compared by individual website, ranging in grade level from 9.2 to 15.2. Only 10 articles (9%) were written below a sixth-grade level and these tended to discuss simpler topics. Patient-directed online information about lung cancer exceeds the recommended sixth-grade reading level. Readability varies between individual websites, allowing physicians to direct patients according to level of health literacy. Modifications to existing materials can significantly improve readability while maintaining content for patients with low health literacy. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Children's understanding of cancer and views on health-related behaviour: a 'draw and write' study.

    Science.gov (United States)

    Knighting, K; Rowa-Dewar, N; Malcolm, C; Kearney, N; Gibson, F

    2011-03-01

    Few studies have explored young children's understanding of cancer and health-related behaviours yet this is essential to develop health promotion initiatives that build on young children's current knowledge levels and awareness. An exploratory descriptive design using the 'draw and write' technique was used to investigate children's views of cancer and health behaviours. The sample included 195 children aged eight to 11 years from five schools in deprived, affluent and rural locations in Scotland. When asked about cancer children demonstrated a good level of awareness by responding with text and drawings about the what they understood cancer to be; types of cancer; causes of cancer; what happens to people who have cancer; their personal experience of cancer and the emotions they associated with cancer. Older children, and children attending affluent schools, have more defined ideas about the causes of cancer and awareness of broader issues such as the risk of passive smoking or the potential impact on the family. Factors such as alcohol and illegal drugs were only reported by children attending schools in deprived locations. Children demonstrated considerable knowledge about healthy and unhealthy lifestyle behaviours; however, it is not clear whether this knowledge translates into their behaviours or the choices offered within their home environment. Children view cancer in a negative way from an early age, even without personal experience. There is a need to demystify cancer in terms of its causes, how to recognize it, how it is treated and to publicize improved survival rates. There is a need for targeted and developmentally appropriate approaches to be taken to health education in schools, with an awareness of the influence of the media on children's information. Strategies should take into consideration the socio-economic and cultural contexts of children's lives which influence their choices and behaviours. © 2010 Blackwell Publishing Ltd.

  20. Glycosylation-mediated phenylpropanoid partitioning in Populus tremuloides cell cultures

    Directory of Open Access Journals (Sweden)

    Babst Benjamin A

    2009-12-01

    Full Text Available Abstract Background Phenylpropanoid-derived phenolic glycosides (PGs and condensed tannins (CTs comprise large, multi-purpose non-structural carbon sinks in Populus. A negative correlation between PG and CT concentrations has been observed in several studies. However, the molecular mechanism underlying the relationship is not known. Results Populus cell cultures produce CTs but not PGs under normal conditions. Feeding salicyl alcohol resulted in accumulation of salicins, the simplest PG, in the cells, but not higher-order PGs. Salicin accrual reflected the stimulation of a glycosylation response which altered a number of metabolic activities. We utilized this suspension cell feeding system as a model for analyzing the possible role of glycosylation in regulating the metabolic competition between PG formation, CT synthesis and growth. Cells accumulated salicins in a dose-dependent manner following salicyl alcohol feeding. Higher feeding levels led to a decrease in cellular CT concentrations (at 5 or 10 mM, and a negative effect on cell growth (at 10 mM. The competition between salicin and CT formation was reciprocal, and depended on the metabolic status of the cells. We analyzed gene expression changes between controls and cells fed with 5 mM salicyl alcohol for 48 hr, a time point when salicin accumulation was near maximum and CT synthesis was reduced, with no effect on growth. Several stress-responsive genes were up-regulated, suggestive of a general stress response in the fed cells. Salicyl alcohol feeding also induced expression of genes associated with sucrose catabolism, glycolysis and the Krebs cycle. Transcript levels of phenylalanine ammonia lyase and most of the flavonoid pathway genes were reduced, consistent with down-regulated CT synthesis. Conclusions Exogenous salicyl alcohol was readily glycosylated in Populus cell cultures, a process that altered sugar utilization and phenolic partitioning in the cells. Using this system, we

  1. Risk assessment of cancer in relation with radon inhalation

    International Nuclear Information System (INIS)

    Timarche, M.; Laurier, D.; Baysson, H.; Catelinois, O.

    2004-01-01

    Several experimental studies have been studied in France in the field of low exposures to radon. The animal studies confirm the increase of ling cancer risk for exposures less than 100 units of exposures. A synthesis is actually running in the frame of an European programme coordinated by the Laboratory of epidemiology from the Institute of radiation protection and nuclear safety (I.R.S.N.). It will describe the different steps of the carcinogenesis brought into play during this chronic exposure at the level of bronchi epithelium by grouping the whole of data coming from the follow up of uranium miners and experimental studies

  2. Nordic Walking, a therapeutic modality against cancer related fatigue

    OpenAIRE

    González Castro, Cristina

    2014-01-01

    Existe evidencia de que el ejercicio físico puede mejorar los síntomas de los pacientes y supervivientes de cáncer y en especial la fatiga relativa al cáncer (FRC). El Nordic Walking (NW) es una novedosa forma de ejercicio físico que presenta ventajas fisiológicas y psicológicas significativas respecto de la marcha normal. Este artículo propone el NW como tratamiento terapéutico alternativo contra la FRC. There is evidence that physical exercise can improve symptoms in cancer patients and ...

  3. Associations of filaggrin gene loss-of-function variants and human papillomavirus-related cancer and pre-cancer in Danish adults.

    Directory of Open Access Journals (Sweden)

    Tea Skaaby

    Full Text Available Filaggrin proteins are expressed in the skin, oral cavity, oesophagus, and cervical mucose. Loss-of-function mutations in the filaggrin gene (FLG reduce filaggrin expression and cause an impaired skin barrier function. We hypothesized that FLG mutation carriers would be more susceptible to human papillomavirus (HPV infection and thus a higher risk of HPV-related cancer and pre-cancer. We investigated the association of the FLG genotype with incidence of HPV-related cancer of cervix, vagina, vulva, penis, anus and head and neck, and pre-cancer of the cervix.We included 13,376 persons from four population-based studies conducted in the same background population in Copenhagen, Denmark. Participants were genotyped for the most common FLG mutations in Europeans. Information on cancer was obtained from The Danish Cancer Registry until 11 July 2011.There were 489 cases of prevalent and 97 cases of incident HPV-related cancer and pre-cancer (median follow-up 11.5 years. There was a statistically significant association between FLG genotype and incident HPV-related cancer and pre-cancer with a hazard ratio, HR = 2.1 (95% confidence intervals, CI: 1.2, 3.7 for FLG mutation carriers vs. wild types.FLG loss-of-function mutations were associated with higher incidence of HPV-related cancers and pre-cancers that are potentially screening and vaccine preventable.

  4. Development of a tailored work-related support intervention for gastrointestinal cancer patients

    NARCIS (Netherlands)

    Zaman, Anne-Claire G. N. M.; Tytgat, Kristien M. A. J.; Van Hezel, Sanne; Klinkenbijl, Jean H. G.; de Boer, Angela G. E. M.; Frings-Dresen, Monique H. W.

    2017-01-01

    Aim is the development of a work-related support intervention, tailored to the severity of work-related problems of patients diagnosed with gastrointestinal (GI) cancer treated with curative intent. Two methods were used: (1) Work-related problems were identified from the literature and submitted to

  5. PPARgamma-PGC-1alpha activity is determinant of alcohol related breast cancer

    DEFF Research Database (Denmark)

    Koefoed Petersen, Rasmus; Benzon Larsen, Signe; Jensen, Ditte Marie

    2012-01-01

    Alcohol is a risk factor for postmenopausal breast cancer. One of several proposed mechanisms is that alcohol-related breast cancer is caused by increased sex hormone levels. PPARγ inhibits aromatase transcription in breast adipocytes. We reproduced previously found allele-specific effects...... of the wildtype Pro-allele of PPARG Pro12Ala in alcohol related breast cancer. In transiently transfected cells, transcriptional activation by PPARγ and the PPARγ-PGC-1α complex was inhibited by ethanol. PPARγ 12Ala-mediated transcription activation was not enhanced by PGC-1α, resulting in allele......-specific transcription activation by the PPARγ 12Pro-PGC-1α complex. Our results suggest that PPARγ and PGC-1α activity is an important determinant of alcohol related breast cancer....

  6. Age-related cancer mutations associated with clonal hematopoietic expansion

    Science.gov (United States)

    Xie, Mingchao; Lu, Charles; Wang, Jiayin; McLellan, Michael D.; Johnson, Kimberly J.; Wendl, Michael C.; McMichael, Joshua F.; Schmidt, Heather K.; Yellapantula, Venkata; Miller, Christopher A.; Ozenberger, Bradley A.; Welch, John S.; Link, Daniel C.; Walter, Matthew J.; Mardis, Elaine R.; Dipersio, John F.; Chen, Feng; Wilson, Richard K.; Ley, Timothy J.; Ding, Li

    2015-01-01

    Several genetic alterations characteristic of leukemia and lymphoma have been detected in the blood of individuals without apparent hematological malignancies. We analyzed blood-derived sequence data from 2,728 individuals within The Cancer Genome Atlas, and discovered 77 blood-specific mutations in cancer-associated genes, the majority being associated with advanced age. Remarkably, 83% of these mutations were from 19 leukemia/lymphoma-associated genes, and nine were recurrently mutated (DNMT3A, TET2, JAK2, ASXL1, TP53, GNAS, PPM1D, BCORL1 and SF3B1). We identified 14 additional mutations in a very small fraction of blood cells, possibly representing the earliest stages of clonal expansion in hematopoietic stem cells. Comparison of these findings to mutations in hematological malignancies identified several recurrently mutated genes that may be disease initiators. Our analyses show that the blood cells of more than 2% of individuals (5–6% of people older than 70 years) contain mutations that may represent premalignant, initiating events that cause clonal hematopoietic expansion. PMID:25326804

  7. Moxibustion for cancer-related fatigue: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Kim, Mikyung; Kim, Jung-Eun; Lee, Hye-Yoon; Kim, Ae-Ran; Park, Hyo-Ju; Kwon, O-Jin; Kim, Eun-Jung; Park, Yeon-Cheol; Seo, Byung-Kwan; Cho, Jung Hyo; Kim, Joo-Hee

    2017-07-05

    Cancer-related fatigue is one of the most common symptoms experienced by cancer patients, and it diminishes their quality of life. However, there is currently no confirmed standard treatment for cancer-related fatigue, and thus, many patients who suffer cancer-related fatigue seek complementary and alternative medicines such as moxibustion. Moxibustion is one of the most popular therapies in traditional Korean medicine used to manage fatigue. Recent studies have also demonstrated that moxibustion is effective for treating chronic fatigue. However, there is insufficient evidence supporting the effect of moxibustion against cancer-related fatigue. The aim of this study is to assess the efficacy and safety of moxibustion treatment for cancer-related fatigue. A multi-center, three-armed parallel, randomized controlled trial will be conducted. Ninety-six patients with cancer-related fatigue will be recruited from three clinical research centers. They will be randomly allocated to one of three groups in a 1:1:1 ratio. The moxibustion group will receive moxibustion treatment at CV8, CV12, LI4 and ST36. The sham moxibustion group will receive sham moxibustion at non-acupoints. Both the moxibustion and sham moxibustion groups will receive 30-min treatments twice a week for 8 weeks. The usual care group will not receive moxibustion treatment. All participants will be educated via a brochure on how to manage cancer-related fatigue in daily life. The outcome measurements will be evaluated at baseline, week 5, week 9, and week 13 by assessors who are blinded to the group allocation. The primary outcome measure will be the mean change in the average scores of the Brief Fatigue Inventory before and after treatments between groups. The secondary outcome measures will be the mean difference in changes from baseline of the Brief Fatigue Inventory, functional assessments of cancer therapy-fatigue, European Organization for Research and Treatment of Cancer Quality of Life

  8. ICan: an integrated co-alteration network to identify ovarian cancer-related genes.

    Science.gov (United States)

    Zhou, Yuanshuai; Liu, Yongjing; Li, Kening; Zhang, Rui; Qiu, Fujun; Zhao, Ning; Xu, Yan

    2015-01-01

    Over the last decade, an increasing number of integrative studies on cancer-related genes have been published. Integrative analyses aim to overcome the limitation of a single data type, and provide a more complete view of carcinogenesis. The vast majority of these studies used sample-matched data of gene expression and copy number to investigate the impact of copy number alteration on gene expression, and to predict and prioritize candidate oncogenes and tumor suppressor genes. However, correlations between genes were neglected in these studies. Our work aimed to evaluate the co-alteration of copy number, methylation and expression, allowing us to identify cancer-related genes and essential functional modules in cancer. We built the Integrated Co-alteration network (ICan) based on multi-omics data, and analyzed the network to uncover cancer-related genes. After comparison with random networks, we identified 155 ovarian cancer-related genes, including well-known (TP53, BRCA1, RB1 and PTEN) and also novel cancer-related genes, such as PDPN and EphA2. We compared the results with a conventional method: CNAmet, and obtained a significantly better area under the curve value (ICan: 0.8179, CNAmet: 0.5183). In this paper, we describe a framework to find cancer-related genes based on an Integrated Co-alteration network. Our results proved that ICan could precisely identify candidate cancer genes and provide increased mechanistic understanding of carcinogenesis. This work suggested a new research direction for biological network analyses involving multi-omics data.

  9. Cardio-Oncology: An Update on Cardiotoxicity of Cancer-Related Treatment.

    Science.gov (United States)

    Lenneman, Carrie G; Sawyer, Douglas B

    2016-03-18

    Through the success of basic and disease-specific research, cancer survivors are one of the largest growing subsets of individuals accessing the healthcare system. Interestingly, cardiovascular disease is the second leading cause of morbidity and mortality in cancer survivors after recurrent malignancy. This recognition has helped stimulate a collaboration between oncology and cardiology practitioners and researchers, and the portmanteau cardio-oncology (also known as onco-cardiology) can now be found in many medical centers. This collaboration promises new insights into how cancer therapies impact cardiovascular homeostasis and long-term effects on cancer survivors. In this review, we will discuss the most recent views on the cardiotoxicity related to various classes of chemotherapy agents and radiation. We will also discuss broadly the current strategies for treating and preventing cardiovascular effects of cancer therapy. © 2016 American Heart Association, Inc.

  10. Health-Related Quality of Life after Cystectomy and Urinary Diversion for Bladder Cancer

    Science.gov (United States)

    Shih, Cheryl; Porter, Michael P.

    2011-01-01

    With multiple options for urinary diversion after radical cystectomy for bladder cancer that have comparable cancer control and complication rates, health-related quality of life (HRQOL) has become an important consideration. This article reviews the methods for defining HRQOL, the challenges in measuring HRQOL in bladder cancer, and the literature comparing HRQOL after various methods of urinary diversion. Recent contributions include the validation of HRQOL instruments specific to bladder cancer and the publication of several prospective studies measuring HRQOL outcomes after cystectomy and urinary diversion. There is no convincing evidence from existing literature that any particular method of urinary diversion offers superior HRQOL outcomes. Rather, there is growing evidence that good HRQOL can be achieved with patient education and consideration of each patient's clinical and psychosocial situation. Future research should utilize the validated bladder cancer specific HRQOL instruments and perhaps explore the impact of preoperative counseling on postoperative HRQOL. PMID:21826139

  11. Health-Related Quality of Life after Cystectomy and Urinary Diversion for Bladder Cancer

    Directory of Open Access Journals (Sweden)

    Cheryl Shih

    2011-01-01

    Full Text Available With multiple options for urinary diversion after radical cystectomy for bladder cancer that have comparable cancer control and complication rates, health-related quality of life (HRQOL has become an important consideration. This article reviews the methods for defining HRQOL, the challenges in measuring HRQOL in bladder cancer, and the literature comparing HRQOL after various methods of urinary diversion. Recent contributions include the validation of HRQOL instruments specific to bladder cancer and the publication of several prospective studies measuring HRQOL outcomes after cystectomy and urinary diversion. There is no convincing evidence from existing literature that any particular method of urinary diversion offers superior HRQOL outcomes. Rather, there is growing evidence that good HRQOL can be achieved with patient education and consideration of each patient's clinical and psychosocial situation. Future research should utilize the validated bladder cancer specific HRQOL instruments and perhaps explore the impact of preoperative counseling on postoperative HRQOL.

  12. Health-related quality of life and satisfaction with case management in cancer survivors.

    Science.gov (United States)

    Hsu, Ya-Hui; Chai, Hsiu-Ying; Lin, Yu-Fen; Wang, Chao-Hui; Chen, Shu-Ching

    2017-12-01

    To (i) investigate the characteristics of health-related quality of life and satisfaction with case management and (ii) to identify factors associated with health-related quality of life in cancer survivors. The level of health-related quality of life can reflect treatment efficacy and satisfaction with cancer care. A cross-sectional study design was adopted. Subjects from the outpatient setting of a cancer centre in northern Taiwan were recruited by consecutive sampling. A set of questionnaires were employed, including a background information form, case management service satisfaction survey (CMSS) and The European Quality of Life Scale (EQ-5D). Descriptive statistics were used to examine levels of health-related quality of life and satisfaction with case management. Pearson's correlation was used to identify relationships between treatment characteristics, satisfaction with case management and health-related quality of life. Multiple stepwise regression was used to identify factors associated with health-related quality of life. A total of 252 cancer patients were recruited. The three lowest scores for items of health-related quality of life were mobility, self-care and usual activities. Cancer survivors with higher mobility, less pain and discomfort, and lower anxiety and depression were more likely to have better health-related quality of life. Mobility, pain and discomfort, and anxiety and depression are important predictive factors of high health-related quality of life in cancer survivors. In clinical care, patients' physical mobility, pain and discomfort, and anxiety and depression are important indicators of health-related quality of life. Case managers should include self-care and symptom management into survivorship care plans to improve health-related quality of life during survival after treatment concludes. © 2017 John Wiley & Sons Ltd.

  13. 'Good’ palliative primary care according to advanced cancer patients and their relatives: an interview study on needs.

    NARCIS (Netherlands)

    Donker, G.A.; Rijken, P.M.; Korevaar, J.C.; Custers, J.; Hofstede, J.; Francke, A.L.

    2017-01-01

    Background: Cancer causes approximately one third of all deaths in industrialized countries. Hence advanced cancer patients and their relatives are a main target group of palliative care. Methods: In qualitative interviews with 13 Dutch patients and 14 relatives confronted with advanced cancer

  14. Perceived impact of cancer among adolescents and young adults: Relationship with health-related quality of life and distress

    NARCIS (Netherlands)

    Husson, O.; Zebrack, B.J.

    2017-01-01

    OBJECTIVE: To examine whether perceptions of the impact of cancer are related to health-related quality of life (HRQoL) and psychological distress among survivors of cancer in adolescence and young adulthood (AYA). METHODS: One hundred seventy-three AYA cancer survivors (aged 18-35 and 15-29 years

  15. Childhood cancer mortality in relation to the St Lucie nuclear power station

    International Nuclear Information System (INIS)

    Boice, John D Jr; Mumma, Michael T; Blot, William J; Heath, Clark W Jr

    2005-01-01

    An unusual county-wide excess of childhood cancers of brain and other nervous tissue in the late 1990s in St Lucie County, Florida, prompted the Florida Department of Health to conduct a case-control study within the county assessing residential chemical exposures. No clear associations were found, but claims were then made that the release of radioactive substances such as strontium 90 from the St Lucie nuclear power station, which began operating in 1976, might have played a role. To test the plausibility of this hypothesis, we extended by 17 years a previous study of county mortality conducted by the National Cancer Institute. Rates of total cancer, leukaemia and cancer of brain and other nervous tissue in children and across all ages in St Lucie County were evaluated with respect to the years before and after the nuclear power station began operation and contrasted with rates in two similar counties in Florida (Polk and Volusia). Over the prolonged period 1950-2000, no unusual patterns of childhood cancer mortality were found for St Lucie County as a whole. In particular, no unusual patterns of childhood cancer mortality were seen in relation to the start-up of the St Lucie nuclear power station in 1976. Further, there were no significant differences in mortality between the study and comparison counties for any cancer in the time period after the power station was in operation. Relative rates for all childhood cancers and for childhood leukaemia were higher before the nuclear facility began operating than after, while rates of brain and other nervous tissue cancer were slightly lower in St Lucie County than in the two comparison counties for both time periods. Although definitive conclusions cannot be drawn from descriptive studies, these data provide no support for the hypothesis that the operation of the St Lucie nuclear power station has adversely affected the cancer mortality experience of county residents

  16. Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation.

    Science.gov (United States)

    Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian; Wagtberg Sen, Jette; Rasmussen, Søren Kofoed; Kontoravdi, Cleo; Weilguny, Dietmar; Andersen, Mikael Rørdam

    2015-03-01

    Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in the biopharmaceutical industry. Amino acid and glucose consumption, cell growth, metabolism, antibody titer, and N-glycosylation patterns are always the major concerns during upstream process optimization, especially media optimization. Gaining knowledge on their interrelations could provide insight for obtaining higher immunoglobulin G (IgG) titer and better controlling glycosylation-related product quality. In this work, different fed-batch processes with two chemically defined proprietary media and feeds were studied using two IgG-producing cell lines. Our results indicate that the balance of glucose and amino acid concentration in the culture is important for cell growth, IgG titer and N-glycosylation. Accordingly, the ideal fate of glucose and amino acids in the culture could be mainly towards energy and recombinant product, respectively. Accumulation of by-products such as NH4(+) and lactate as a consequence of unbalanced nutrient supply to cell activities inhibits cell growth. The levels of Leu and Arg in the culture, which relate to cell growth and IgG productivity, need to be well controlled. Amino acids with the highest consumption rates correlate with the most abundant amino acids present in the produced IgG, and thus require sufficient availability during culture. Case-by-case analysis is necessary for understanding the effect of media and process optimization on glycosylation. We found that in certain cases the presence of Man5 glycan can be linked to limitation of UDP-GlcNAc biosynthesis as a result of insufficient extracellular Gln. However, under different culture conditions, high Man5 levels can also result from low α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (GnTI) and UDP-GlcNAc transporter activities, which may be attributed to high level of NH4+ in the cell culture. Furthermore, galactosylation of the mAb Fc glycans

  17. Crystallization and preliminary crystallographic analysis of human glycosylated haemoglobin

    International Nuclear Information System (INIS)

    Syakhovich, Vitaly E.; Saraswathi, N. T.; Ruff, Marc; Bokut, Sergey B.; Moras, Dino

    2006-01-01

    Non enzymatic modification of haemoglobin by glucose plays an important role in diabetes pathogenesis. Here the purification, characterization and crystallization of human glycosylated haemoglobin are reported. Human glycosylated haemoglobin A 1C is a stable minor variant formed in vivo by post-translational modification of the main form of haemoglobin by glucose. Crystals of oxyHbA 1C were obtained using the hanging-drop vapour-diffusion method and PEG as precipitant. The diffraction pattern of the crystal extends to a resolution of 2.3 Å at 120 K. The crystals belong to space group C2, with unit-cell parameters a = 237.98, b = 59.27, c = 137.02 Å, α = 90.00, β = 125.40, γ = 90.00°. The presence of two and a half molecules per asymmetric unit gives a crystal volume per protein weight (V M ) of 9.70 Å 3 Da −1 and a solvent content of 49%

  18. Crystallization and preliminary crystallographic analysis of human glycosylated haemoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Syakhovich, Vitaly E. [Department of Biochemistry and Biophysics, International Sakharov Environmental University, Dolgobrodskaya St 23, 220009 Minsk (Belarus); Saraswathi, N. T.; Ruff, Marc, E-mail: ruff@igbmc.u-strasbg.fr [Département de Biologie et Génomique Structurales, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch (France); Bokut, Sergey B. [Department of Biochemistry and Biophysics, International Sakharov Environmental University, Dolgobrodskaya St 23, 220009 Minsk (Belarus); Moras, Dino [Département de Biologie et Génomique Structurales, Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 Rue Laurent Fries, BP 10142, 67404 Illkirch (France); Department of Biochemistry and Biophysics, International Sakharov Environmental University, Dolgobrodskaya St 23, 220009 Minsk (Belarus)

    2006-02-01

    Non enzymatic modification of haemoglobin by glucose plays an important role in diabetes pathogenesis. Here the purification, characterization and crystallization of human glycosylated haemoglobin are reported. Human glycosylated haemoglobin A{sub 1C} is a stable minor variant formed in vivo by post-translational modification of the main form of haemoglobin by glucose. Crystals of oxyHbA{sub 1C} were obtained using the hanging-drop vapour-diffusion method and PEG as precipitant. The diffraction pattern of the crystal extends to a resolution of 2.3 Å at 120 K. The crystals belong to space group C2, with unit-cell parameters a = 237.98, b = 59.27, c = 137.02 Å, α = 90.00, β = 125.40, γ = 90.00°. The presence of two and a half molecules per asymmetric unit gives a crystal volume per protein weight (V{sub M}) of 9.70 Å{sup 3} Da{sup −1} and a solvent content of 49%.

  19. Glycosylated yellow laccases of the basidiomycete Stropharia aeruginosa.

    Science.gov (United States)

    Daroch, Maurycy; Houghton, Catharine A; Moore, Jonathan K; Wilkinson, Mark C; Carnell, Andrew J; Bates, Andrew D; Iwanejko, Lesley A

    2014-05-10

    Here we describe the identification, purification and characterisation of glycosylated yellow laccase proteins from the basidiomycete fungus Stropharia aeruginosa. Biochemical characterisation of two yellow laccases, Yel1p and Yel3p, show that they are both secreted, monomeric, N-glycosylated proteins of molecular weight around 55kDa with substrate specificities typical of laccases, but lacking the absorption band at 612nm typical of the blue laccase proteins. Low coverage, high throughput 454 transcriptome sequencing in combination with inverse-PCR was used to identify cDNA sequences. One of the cDNA sequences has been assigned to the Yel1p protein on the basis of identity between the translated protein sequence and the peptide data from the purified protein, and the full length gene sequence has been obtained. Biochemical properties, substrate specificities and protein sequence data have been used to discuss the unusual spectroscopic properties of S. aeruginosa proteins in the context of recent theories about the differences between yellow and blue laccases. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Novel drugs that target the estrogen-related receptor alpha: their therapeutic potential in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    May, Felicity EB, E-mail: F.E.B.May@ncl.ac.uk [Northern Institute for Cancer Research and Department of Pathology, Faculty of Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne (United Kingdom)

    2014-05-23

    The incidence of breast cancer continues to rise: 1.7 million women were diagnosed with and 521,000 women died from breast cancer in 2012. This review considers first current treatment options: surgery; radiotherapy; and systemic endocrine, anti-biological, and cytotoxic therapies. Clinical management includes prevention, early detection by screening, treatment with curative intent, management of chronic disease, and palliative control of advanced breast cancer. Next, the potential of novel drugs that target DNA repair, growth factor dependence, intracellular and intercellular signal transduction, and cell cycle are considered. Estrogen-related receptor alpha has attracted attention as a therapeutic target in triple-negative breast cancers with de novo resistance to, and in breast cancers with acquired resistance to, endocrine therapies such as antiestrogens and aromatase inhibitors. Estrogen-related receptor alpha is an orphan receptor and transcription factor. Its activity is regulated by coregulator proteins and posttranslational modification. It is an energy sensor that controls adaptation to energy demand and may facilitate glycolytic metabolism and mitochondrial oxidative respiration in breast cancer cells. Estrogen-related receptor alpha increases breast cancer cell migration, proliferation, and tumor development. It is expressed at high levels in estrogen receptor-negative tumors, and is proposed to activate estrogen-responsive genes in endocrine-resistant tumors. The structures and functions of the ligand-binding domains of estrogen receptor alpha and estrogen-related receptor alpha, their ability to bind estrogens, phytoestrogens, and synthetic ligands, and the effects of ligand agonists, antagonists, and inverse agonists on biological activity, are evaluated. Synthetic ligands of estrogen-related receptor alpha have activity in preclinical models of metabolic disorders, diabetes, osteoporosis, and oncology. The clinical settings in which these novel

  1. Novel drugs that target the estrogen-related receptor alpha: their therapeutic potential in breast cancer

    International Nuclear Information System (INIS)

    May, Felicity EB

    2014-01-01

    The incidence of breast cancer continues to rise: 1.7 million women were diagnosed with and 521,000 women died from breast cancer in 2012. This review considers first current treatment options: surgery; radiotherapy; and systemic endocrine, anti-biological, and cytotoxic therapies. Clinical management includes prevention, early detection by screening, treatment with curative intent, management of chronic disease, and palliative control of advanced breast cancer. Next, the potential of novel drugs that target DNA repair, growth factor dependence, intracellular and intercellular signal transduction, and cell cycle are considered. Estrogen-related receptor alpha has attracted attention as a therapeutic target in triple-negative breast cancers with de novo resistance to, and in breast cancers with acquired resistance to, endocrine therapies such as antiestrogens and aromatase inhibitors. Estrogen-related receptor alpha is an orphan receptor and transcription factor. Its activity is regulated by coregulator proteins and posttranslational modification. It is an energy sensor that controls adaptation to energy demand and may facilitate glycolytic metabolism and mitochondrial oxidative respiration in breast cancer cells. Estrogen-related receptor alpha increases breast cancer cell migration, proliferation, and tumor development. It is expressed at high levels in estrogen receptor-negative tumors, and is proposed to activate estrogen-responsive genes in endocrine-resistant tumors. The structures and functions of the ligand-binding domains of estrogen receptor alpha and estrogen-related receptor alpha, their ability to bind estrogens, phytoestrogens, and synthetic ligands, and the effects of ligand agonists, antagonists, and inverse agonists on biological activity, are evaluated. Synthetic ligands of estrogen-related receptor alpha have activity in preclinical models of metabolic disorders, diabetes, osteoporosis, and oncology. The clinical settings in which these novel

  2. Lympho-vascular invasion in BRCA related breast cancer compared to sporadic controls

    International Nuclear Information System (INIS)

    Voss, Marise R Heerma van; Groep, Petra van der; Bart, Jos; Wall, Elsken van der; Diest, Paul J van

    2010-01-01

    Germline mutations in the BRCA1 gene predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumors is important for selecting patients for genetic screening and provides inside in carcinogenetic pathways. Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels and are often of the medullary (like) type that is known to have a low rate of lympho-vascular invasion (LVI), we hypothesized that absence of LVI could characterize BRCA1 related breast cancer. A population of 68 BRCA1 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumor type. LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P = 0.54, OR = 1.29, CI 0.58-2.78). LVI is frequent in BRCA1 germline mutation related breast cancers, but seems to occur as often in sporadic controls matched for age, grade and tumor type. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation

  3. Lympho-vascular invasion in BRCA related breast cancer compared to sporadic controls

    Directory of Open Access Journals (Sweden)

    van der Wall Elsken

    2010-04-01

    Full Text Available Abstract Background Germline mutations in the BRCA1 gene predispose to the development of breast cancer, exhibiting a specific histological phenotype. Identification of possible hallmarks of these tumors is important for selecting patients for genetic screening and provides inside in carcinogenetic pathways. Since BRCA1-associated breast cancers have pushing borders that prevent them from easily reaching vessels and are often of the medullary (like type that is known to have a low rate of lympho-vascular invasion (LVI, we hypothesized that absence of LVI could characterize BRCA1 related breast cancer. Methods A population of 68 BRCA1 related invasive breast cancers was evaluated for LVI by an experienced breast pathologist blinded to mutation status, and compared to a control group matched for age, grade and tumor type. Results LVI was present in 25.0% of BRCA1 related cases, compared to 20.6% of controls (P = 0.54, OR = 1.29, CI 0.58-2.78. Conclusion LVI is frequent in BRCA1 germline mutation related breast cancers, but seems to occur as often in sporadic controls matched for age, grade and tumor type. Apparently, these hereditary cancers find their way to the blood and lymph vessels despite their well demarcation and often medullary differentiation.

  4. Dyadic associations between cancer-related stress and fruit and vegetable consumption among colorectal cancer patients and their family caregivers.

    Science.gov (United States)

    Shaffer, Kelly M; Kim, Youngmee; Llabre, Maria M; Carver, Charles S

    2016-02-01

    This study examined how stress from cancer affects fruit and vegetable consumption (FVC) in cancer patients and their family caregivers during the year following diagnosis. Colorectal cancer patients and their caregivers (92 dyads) completed questionnaires at two (T1), six (T2), and 12 months post-diagnosis (T3). Individuals reported perceived cancer-related stress (CRS) at T1 and days of adequate FVC at T1 through T3. Both patients and caregivers reported inadequate FVC during the first year post-diagnosis. Latent growth modeling with actor-partner interdependence modeling revealed that, at T1, one's own greater CRS was associated with one's partner having fewer concurrent days of adequate FVC (ps = .01). Patients' greater CRS predicted their own more pronounced rebound pattern in FVC (p = .01); both patients' and caregivers' CRS marginally predicted their partners' change in FVC (p = .09). Findings suggest that perceived stress from cancer hinders FVC around the diagnosis, but motivates positive dietary changes by the end of the first year.

  5. Expression of emotions related to the experience of cancer in younger and older Arab breast cancer survivors.

    Science.gov (United States)

    Goldblatt, Hadass; Cohen, Miri; Azaiza, Faisal

    2016-12-01

    Researchers have suggested that older adults express less negative emotions. Yet, emotional expression patterns in older and younger breast cancer survivors, have barely been examined. This study aimed to explore types and intensity of negative and positive emotional expression related to the breast cancer experience by younger and older Arab breast cancer survivors. Participants were 20 younger (aged 32-50) and 20 older (aged 51-75) Muslim and Christian Arab breast cancer survivors (stages I-III), currently free of disease. Data were gathered through in-depth semi-structured interviews. Mixed methods analyses were conducted, including: (1) frequency analysis of participants' emotional expressions; (2) content analysis of emotional expressions, categorized according to negative and positive emotions. Three emotional expression modalities were revealed: (1) Succinct versus comprehensive accounts; (2) expression of emotions versus avoidance of emotions; (3) patterns of expression of positive emotions and a sense of personal growth. Younger women provided more detailed accounts about their illness experiences than older women. Older women's accounts were succinct, action-focused, and included more emotion-avoiding expressions than younger women. Understanding the relationships between emotional expression, emotional experience, and cancer survivors' quality of life, specifically of those from traditional communities, is necessary for developing effective psycho-social interventions.

  6. Cancer-Related Fatigue in Women With Breast Cancer: Outcomes of a 5-Year Prospective Cohort Study.

    LENUS (Irish Health Repository)

    Goldstein, David

    2012-04-16

    PURPOSEProlonged and disabling fatigue is prevalent after cancer treatment, but the early natural history of cancer-related fatigue (CRF) has not been systematically examined to document consistent presence of symptoms. Hence, relationships to cancer, surgery, and adjuvant therapy are unclear. PATIENTS AND METHODSA prospective cohort study of women receiving adjuvant treatment for early-stage breast cancer was conducted. Women (n = 218) were enrolled after surgery and observed at end treatment and at 1, 3, 6, 9, and 12 months as well as 5 years. Structured interviews and self-report questionnaires were used to record physical and psychologic health as well as disability and health care utilization. Patients with CRF persisting for 6 months were assessed to exclude alternative medical and psychiatric causes of fatigue. Predictors of persistent fatigue, mood disturbance, and health care utilization were sought by logistic regression.ResultsThe case rate for CRF was 24% (n = 51) postsurgery and 31% (n = 69) at end of treatment; it became persistent in 11% (n = 24) at 6 months and 6% (n = 12) at 12 months. At each time point, approximately one third of the patients had comorbid mood disturbance. Persistent CRF was predicted by tumor size but not demographic, psychologic, surgical, or hematologic parameters. CRF was associated with significant disability and health care utilization. CONCLUSIONCRF is common but generally runs a self-limiting course. Much of the previously reported high rates of persistent CRF may be attributable to factors unrelated to the cancer or its treatment.

  7. The Progress of T Cell Immunity Related to Prognosis in Gastric Cancer.

    Science.gov (United States)

    Wei, Ming; Shen, Duo; Mulmi Shrestha, Sachin; Liu, Juan; Zhang, Junyi; Yin, Ying

    2018-01-01

    Gastric cancer is the fifth most common malignancy all over the world, and the factors that can affect progress and prognosis of the gastric cancer patients are various, such as TNM stages, invasive depth, and lymph node metastasis ratio. T cell immunity is important component of human immunity system and immunity responding to tumor and dysfunction or imbalance of T cell immunity will lead to serious outcomes for body. T cell immunity includes many different types of cells, CD4+ T cell, CD8+ T cell, memory cell, and so on, and each of them has special function on antitumor response or tumor immune escape which is revealed in lung cancer, colorectal cancer, breast cancer, ovarian cancer, and so on. But its correlation with gastric cancer is not clear. Our review was preformed to explore the relationship between the progress and prognosis of gastric cancer (GC) and T cell immunity. According to recent researches, T cell immunity may have an important role in the progress and prognosis of GCs, but its function is affected by location, category, related molecule, and interaction between the cells, and some effects still are controversial. More researches are needed to clarify this correlation.

  8. Kallikrein-related peptidase 7 is a potential target for the treatment of pancreatic cancer

    Science.gov (United States)

    Zheng, Jun; Zhang, Ding; Liu, Wei; Zheng, Wei Hong; Li, Xiao Song; Yao, Ru Cheng; Wang, Fangyu; Liu, Sen; Tan, Xiao

    2018-01-01

    Pancreatic cancer is one of the deadliest cancers with very poor prognosis, and the five-year survival rate of the patients is less than 5% after diagnosis. Kallikrein-related peptidases (KLKs) belong to a serine protease family with 15 members that play important roles in cellular physiological behavior and diseases. The high expression level of KLK7 in pancreatic cancer tissues is considered to be a marker for the poor prognosis of this disease. In this work, we set out to investigate whether KLK7 could be a target for the treatment of pancreatic cancer. Short hairpin RNAs (shRNAs) were designed and constructed in lentivirus to knock down KLK7 in pancreatic cancer cell line PANC-1, and the real time cellular analysis (RTCA) was used to evaluate cell proliferation, migration and invasion abilities. Small molecules inhibiting KLK7 were discovered by computer-aided drug screening and used to inhibit PANC-1 cells. Our results confirmed that KLK7 is significantly up-regulated in pancreatic cancer tissue, and knocking down or inhibiting KLK7 efficiently inhibited the proliferation, migration and invasion of pancreatic cancer cells. This study suggested that KLK7 could be a potential chemotherapy target for treatment of pancreatic cancer, which would provide us a novel strategy for the treatment of this disease. PMID:29560118

  9. Circulating DNA and its methylation level in inflammatory bowel disease and related colon cancer.

    Science.gov (United States)

    Bai, Xuming; Zhu, Yaqun; Pu, Wangyang; Xiao, Li; Li, Kai; Xing, Chungen; Jin, Yong

    2015-01-01

    Both of chronic inflammation and abnormal immune in inflammatory bowel disease can induce colon cancer. Previous research showed that cell apoptosis and necrosis become the main source of circulating DNA in the peripheral blood during tumorigenesis that reduced along with methylation degree. However, its role in the process of colitis transforming to colon cancer is not clarified. Drinking 3% DSS was used to establish colitis model, while 3% dextran sodium sulfate (DSS) combined with azo oxidation methane (AOM) intraperitoneal injection was applied to establish colitis related colon cancer model. Circulating DNA and its methylation level in peripheral blood were tested. Morphology observation, HE staining, and p53 and β-catenin expression detection confirmed that drinking 3% DSS and 3% DSS combined with AOM intraperitoneal injection can successfully establish colitis and colitis associated colorectal cancer models. Circulating DNA level in colitis and colon cancer mice increased by gradient compared with control, while significant difference was observed between each other. Circulating DNA methylation level decreased obviously in colitis and colon cancer, and significant difference was observed between each other. Abnormal protein expression, circulating DNA and its methylation level in ulcerative colitis associated colorectal tissues change in gradient, suggesting that circulating DNA and its methylation level can be treated as new markers for colitis cancer transformation that has certain significance to explore the mechanism of human ulcerative colitis canceration.

  10. Knowledge and Practices Related to Screening for Breast Cancer among Women in Delhi, India

    Science.gov (United States)

    Dahiya, Neha; Basu, Saurav; Singh, Megha Chandra; Garg, Suneela; Kumar, Rajesh; Kohli, Charu

    2018-01-27

    Background: Breast cancer is a major public health problem globally. The ongoing epidemiological, socio-cultural and demographic transition by accentuating the associated risk factors has disproportionately increased the incidence of breast cancer cases and resulting mortality in developing countries like India. Early diagnosis with rapid initiation of treatment reduces breast cancer mortality. Therefore awareness of breast cancer risk and a willingness to undergo screening are essential. The objective of the present study was to assess the knowledge and practices relating to screening for breast cancer among women in Delhi. Methods: Data were obtained from 222 adult women using a pretested selfadministered questionnaire. Results: Rates for knowledge of known risk factors of breast cancer were: family history of breast cancer, 59.5%; smoking, 57.7%; old age, 56.3%; lack of physical exercise, 51.9%; lack of breastfeeding, 48.2%; late menopause, 37.4%; and early menarche, 34.7%. Women who were aged awareness generation among adult women regarding risk factors and methods for early detection of breast cancer. Creative Commons Attribution License

  11. How much do cancer-related symptoms contribute to health-related quality of life in lung and colorectal cancer patients? A report from the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium.

    Science.gov (United States)

    Kenzik, Kelly M; Ganz, Patricia A; Martin, Michelle Y; Petersen, Laura; Hays, Ron D; Arora, Neeraj; Pisu, Maria

    2015-08-15

    The objective of this study was to examine associations of symptoms with physical and mental health-related quality of life (HRQOL) in patients with colorectal cancer (CRC) and in patients with lung cancer. Patients with newly diagnosed CRC (n = 3040) or lung cancer (n = 2297) who were participating in the Cancer Care Outcomes Research and Surveillance Consortium study completed surveys on general HRQOL and symptoms. HRQOL was measured by using physical component summary (PCS) and mental component summary (MCS) scores on the Medical Outcomes Study 12-item short-form heath survey. Nonspecific cancer symptoms were measured using items from the European Organization for Research and Treatment of Cancer core quality-of-life questionnaire. Cancer type-specific modules developed by the European Organization for Research and Treatment of Cancer were used to assess CRC-specific and lung cancer-specific symptoms. For both cancer types, linear regression models that were controlled for demographic and clinical information were used to examine correlations of nonspecific and cancer-specific symptoms with PCS and MCS scores. PCS scores for patients with CRC and lung cancer were below the general population norm of 50 (43 and 37, respectively), and MCS scores were at the population norm. For the CRC sample, in the model that included both symptom indices, an increase in nonspecific symptoms was more strongly associated with lower PCS and MCS scores than an increase in CRC-specific symptoms (PCS, standardized coefficient [β] = -0.41 vs -0.09; MCS, β = -0.38 vs -0.08). In a similar model for lung cancer, increases in lung cancer-specific symptoms were more strongly associated with lower PCS scores (β = -0.34 vs -0.20), whereas nonspecific symptoms were more strongly associated with lower MCS scores (β = -0.34 vs -0.14). Symptoms were associated with HRQOL impairments in recently diagnosed patients. Additional supportive care implemented early in cancer care

  12. Bayesian spatio-temporal modelling of tobacco-related cancer mortality in Switzerland

    Directory of Open Access Journals (Sweden)

    Verena Jürgens

    2013-05-01

    Full Text Available Tobacco smoking is a main cause of disease in Switzerland; lung cancer being the most common cancer mortality in men and the second most common in women. Although disease-specific mortality is decreasing in men, it is steadily increasing in women. The four language regions in this country might play a role in this context as they are influenced in different ways by the cultural and social behaviour of neighbouring countries. Bayesian hierarchical spatio-temporal, negative binomial models were fitted on subgroup-specific death rates indirectly standardized by national references to explore age- and gender-specific spatio-temporal patterns of mortality due to lung cancer and other tobacco-related cancers in Switzerland for the time period 1969-2002. Differences influenced by linguistic region and life in rural or urban areas were also accounted for. Male lung cancer mortality was found to be rather homogeneous in space, whereas women were confirmed to be more affected in urban regions. Compared to the German-speaking part, female mortality was higher in the French-speaking part of the country, a result contradicting other reports of similar comparisons between France and Germany. The spatio-temporal patterns of mortality were similar for lung cancer and other tobacco-related cancers. The estimated mortality maps can support the planning in health care services and evaluation of a national tobacco control programme. Better understanding of spatial and temporal variation of cancer of the lung and other tobacco-related cancers may help in allocating resources for more effective screening, diagnosis and therapy. The methodology can be applied to similar studies in other settings.

  13. Support for food policy initiatives is associated with knowledge of obesity-related cancer risk factors

    Directory of Open Access Journals (Sweden)

    Wendy Watson

    2017-12-01

    Full Text Available Objectives: To investigate community support for government-led policy initiatives to positively influence the food environment, and to identify whether there is a relationship between support for food policy initiatives and awareness of the link between obesity-related lifestyle risk factors and cancer. Methods: An online survey of knowledge of cancer risk factors and attitudes to policy initiatives that influence the food environment was completed by 2474 adults from New South Wales, Australia. The proportion of participants in support of seven food policy initiatives was quantified in relation to awareness of the link between obesity, poor diet, insufficient fruit and vegetable consumption, and physical inactivity with cancer and other health conditions. Results: Overall, policies that involved taxing unhealthy foods received the least support (41.5%. Support was highest for introducing a colour-coded food labelling system (85.9%, restricting claims being made about the health benefits of foods which are, overall, unhealthy (82.6%, displaying health warning labels on unhealthy foods (78.7% and banning unhealthy food advertising that targets children (72.6%. Participants who were aware that obesity-related lifestyle factors are related to cancer were significantly more likely to support food policy initiatives than those who were unaware. Only 17.5% of participants were aware that obesity, poor diet, insufficient fruit and vegetable consumption, and physical inactivity are linked to cancer. Conclusions: There is strong support for all policies related to food labelling and a policy banning unhealthy food advertising to children. Support for food policy initiatives that positively influence the food environment was higher among those who were aware of the link between cancer and obesity-related lifestyle factors than among those who were unaware of this link. Increasing awareness of the link between obesity-related lifestyle factors and cancer

  14. MeInfoText 2.0: gene methylation and cancer relation extraction from biomedical literature

    Directory of Open Access Journals (Sweden)

    Fang Yu-Ching

    2011-12-01

    Full Text Available Abstract Background DNA methylation is regarded as a potential biomarker in the diagnosis and treatment of cancer. The relations between aberrant gene methylation and cancer development have been identified by a number of recent scientific studies. In a previous work, we used co-occurrences to mine those associations and compiled the MeInfoText 1.0 database. To reduce the amount of manual curation and improve the accuracy of relation extraction, we have now developed MeInfoText 2.0, which uses a machine learning-based approach to extract gene methylation-cancer relations. Description Two maximum entropy models are trained to predict if aberrant gene methylation is related to any type of cancer mentioned in the literature. After evaluation based on 10-fold cross-validation, the average precision/recall rates of the two models are 94.7/90.1 and 91.8/90% respectively. MeInfoText 2.0 provides the gene methylation profiles of different types of human cancer. The extracted relations with maximum probability, evidence sentences, and specific gene information are also retrievable. The database is available at http://bws.iis.sinica.edu.tw:8081/MeInfoText2/. Conclusion The previous version, MeInfoText, was developed by using association rules, whereas MeInfoText 2.0 is based on a new framework that combines machine learning, dictionary lookup and pattern matching for epigenetics information extraction. The results of experiments show that MeInfoText 2.0 outperforms existing tools in many respects. To the best of our knowledge, this is the first study that uses a hybrid approach to extract gene methylation-cancer relations. It is also the first attempt to develop a gene methylation and cancer relation corpus.

  15. Prognosis of breast cancer is associated with one-carbon metabolism related nutrients among Korean women

    Directory of Open Access Journals (Sweden)

    Lee Yunhee

    2012-08-01

    Full Text Available Abstract Background The 5-year survival rate for breast cancer among Korean women has increased steadily; however, breast cancer remains the leading cause of cancer mortality among women. One-carbon metabolism, which requires an adequate supply of methyl group donors and B vitamins, may affect the prognosis of breast cancer. This aim of this study was to investigate the associations of dietary intake of vitamin B2, vitamin B6 and folate before diagnosis on the prognosis of breast cancer. Methods We assessed the dietary intake using a food frequency questionnaire with 980 women who were newly diagnosed and histopathologically confirmed to have primary breast cancer from hospitals in Korea, and 141 disease progression events occurred. Cox’s proportional hazard regression models were used to estimate the hazard ratio (HR and 95% confidence interval (95% CI adjusting for age, education, recruitment sites, TNM stage, hormone status, nuclear grade and total calorie. Results There was no significant association between any one-carbon metabolism related nutrients (vitamin B2, B6 and folate and the progression of breast cancer overall. However, one-carbon metabolism related nutrients were associated with disease progression in breast cancer patients stratified by subtypes. In ER + and/or PR + breast cancers, no association was observed; however, in ER–/PR– breast cancers, a high intake of vitamin B2 and folate statistically elevated the HR of breast cancer progression (HR = 2.28; 95% CI, 1.20-4.35, HR = 1.84; 95% CI, 1.02-3.32, respectively compared to a low intake. This positive association between the ER/PR status and progression of the disease was profound when the nutrient intakes were categorized in a combined score (Pinteraction = 0.018. In ER–/PR– breast cancers, high combined scores were associated with a significantly poor DFS compared to those belonging to the low score group (HR = 3.84; 95% CI, 1

  16. Dietary intake of nitrate relative to antioxidant vitamin in relation to breast cancer risk: a case-control study.

    Science.gov (United States)

    Yang, Yoon Jung; Hwang, Se Hee; Kim, Hyun Ja; Nam, Seok-Jin; Kong, Gu; Kim, Mi Kyung

    2010-01-01

    Nitrate is a precursor in the endogenous formation of N-nitroso compounds, which are potent animal carcinogens, whereas antioxidant vitamins have been suggested to protect against carcinogenesis. Interestingly, nitrate and antioxidant vitamins stem from the same dietary sources. We investigated whether the intake of nitrate relative to antioxidant vitamins is associated with the risk of breast cancer. A total of 362 breast cancer cases were matched to the 362 controls by age and menopausal status. Dietary intake was assessed using a quantitative food frequency questionnaire with 121 food items by trained interviewers. The nitrate to antioxidant vitamin consumption ratio was then calculated. Conditional logistic regression analysis was used to obtain odds ratios (ORs) and corresponding 95% confidence intervals (CI). Mean intakes of nitrate for cases and controls were 421 mg/day and 424 mg/day, respectively. Intakes of nitrate, nitrate/beta-carotene, nitrate/vitamin C, and nitrate/vitamin E were not associated with breast cancer risk. However, higher breast cancer risk was observed with higher intake of nitrate/folate (OR = 2.03, 95% CI = 1.16-3.54, P for trend = 0.052). Our results suggest that lowering the ratio of nitrate to folate intake may be effective in reducing breast cancer risk.

  17. Depression and Anxiety Symptoms Relate to Distinct Components of Pain Experience among Patients with Breast Cancer

    Directory of Open Access Journals (Sweden)

    Sarah K. Galloway

    2012-01-01

    Full Text Available Breast cancer is a leading cancer diagnosis among women worldwide, with more than 210,000 new cases and 40,000 deaths per year in the United States. Pain, anxiety, and depression can be significant factors during the course of breast cancer. Pain is a complex experience with sensory, affective, and cognitive dimensions. While depression and anxiety symptoms are relatively common among breast cancer patients, little is known about the relation between these psychiatric factors and distinct components of the pain experience. In the present study 60 females presenting to an NCI-designated Cancer Center with newly diagnosed breast cancer completed the Center for Epidemiological Studies 10-item Depression Scale, the State Instrument of the Spielberger State-Trait Anxiety Inventory, and the McGill Pain Questionnaire. Findings indicate that anxiety and depression are common among newly diagnosed breast cancer patients; furthermore, patients experience an appreciable amount of pain even before oncologic treatment starts. State anxiety serves as a predictor of the sensory dimension of the pain experience, whereas depression serves as a predictor of the affective dimension of the pain experience.

  18. Relative and absolute risk models for cancer mortality in ankylosing spondylitis patients

    International Nuclear Information System (INIS)

    Muirhead, C.R.; Darby, S.C.

    1989-01-01

    The updated analyses presented in this paper have indicated that, even after allowing for the effects of other variables, the relative risk of all cancers excluding leukaemia and colon cancer among the irradiated spondylitics tails off beyond twenty-five years following exposure. Additionally, the corresponding absolute excess risk also tails off. This is still the only major study to show a wearing off of the radiation-related risk for such a grouping of cancers (although some wearing off has been seen for individual cancers such as bone in other studies). Further analysis of the spondylitic data (Darby, Doll and Smith, 1988) has not found any artificial explanation for the tailing off in risk, such as changes in lifestyle. However, it is noticeable that the dose was delivered to the spondylitics in fractions (see Lewis et al., 1988, table IV) rather than instantaneously, although it is not immediately obvious why this should have affected the temporal pattern of the risk. (author)

  19. Mutations in TP53 tumor suppressor gene in wood dust-related sinonasal cancer

    DEFF Research Database (Denmark)

    Holmila, Reetta; Bornholdt, Jette; Heikkilä, Pirjo

    2010-01-01

    The causal role of work-related exposure to wood dust in the development of sinonasal cancer has long been established by numerous epidemiologic studies. To study molecular changes in these tumors, we analyzed TP53 gene mutations in 358 sinonasal cancer cases with or without occupational exposure...... affected the ORs only slightly. Smoking did not influence the occurrence of TP53 mutation; however, it was associated with multiple mutations (p = 0.03). As far as we are aware, this is the first study to demonstrate a high prevalence of TP53 mutation-positive cases in a large collection of sinonasal...... cancers with data on occupational exposure. Our results indicate that mutational mechanisms, in particular TP53 mutations, are associated with work-related exposure to wood dust in sinonasal cancer....

  20. Depression and health related quality of life in breast cancer patients

    International Nuclear Information System (INIS)

    Ardebil, M. D.; Bouzari, Z.; Shenas, M. H.; Keighobadi, M.

    2013-01-01

    Objective: To investigate the prevalence of depression in women with breast cancer and relate it to their health-related quality of life. Methods: The cross-sectional study was conducted at the Imam Khomeini Hospital in Iran between January and December 2009, and comprised 60 women with breast cancer with a mean age of 43.8+-47.12 years. In order to assess the health-related quality of life, the study used the parameters of the Iranian version of the Functional Assessment of Cancer Therapy for Breast Cancer. To identify expressive symptoms, the Beck Depression Inventory was used. General linear model regression and SPSS 14 were used to analyse the data. Results: Significant differences in the prevalence of depression between treatment types was found. The presence of depression was significantly correlated with poorer overall health-related quality of life and the four subscales of the protocol. The patients reported statistically significant effects of depression in the overall category (p= 0.001). Participants with depression were more likely to have a poorer overall health-related quality of life, the exception being the social/family well-being subscale. Conclusions: Depression affects health-related quality of life in breast cancer patients. Although further studies are necessary to confirm our findings, but our results emphasise the necessity for better mental health strategies for such patients. (author)

  1. Fab glycosylation of immunoglobulin G does not associate with improvement of rheumatoid arthritis during pregnancy.

    Science.gov (United States)

    Bondt, Albert; Wuhrer, Manfred; Kuijper, T Martijn; Hazes, Johanna M W; Dolhain, Radboud J E M

    2016-11-25

    Changes in immunoglobulin G (IgG) constant domain (Fc) glycosylation are associated with changes in rheumatoid arthritis (RA) disease activity in response to pregnancy. Here, we sought to determine whether the same holds true for variable domain (Fab) glycosylation. IgGs were captured from RA and control sera obtained before (RA only), during and after pregnancy, followed by Fc and Fab separation, glycan release, and mass spectrometric detection. In parallel, glycans from intact IgG were analysed. The data was used to calculate glycosylation traits, and to estimate the level of Fab glycosylation. The overall level of Fab glycosylation was increased in RA patients compared to controls, while no differences in Fab glycosylation patterns were found. For the Fc and intact IgG (Total) previously observed differences in galactosylation and bisection were confirmed. Furthermore, increased galactosylation of Fc and Total were associated with lower disease activity and autoantibody positivity. In addition, the change in Fc galactosylation associated with the change in disease activity during pregnancy and after delivery, while this was not the case for Fab. In contrast to changes in Fc glycosylation, changes in Fab glycosylation are not associated with improvement of RA during pregnancy and arthritis flare after delivery.

  2. Fab glycosylation of immunoglobulin G does not associate with improvement of rheumatoid arthritis during pregnancy

    NARCIS (Netherlands)

    A. Bondt (Albert); M. Wuhrer (Manfred); T.M. Kuijper (Martijn); J.M.W. Hazes (Mieke); R.J.E.M. Dolhain (Radboud)

    2016-01-01

    textabstractBackground: Changes in immunoglobulin G (IgG) constant domain (Fc) glycosylation are associated with changes in rheumatoid arthritis (RA) disease activity in response to pregnancy. Here, we sought to determine whether the same holds true for variable domain (Fab) glycosylation. Methods:

  3. Model-based analysis of N-glycosylation in Chinese hamster ovary cells

    DEFF Research Database (Denmark)

    Krambeck, Frederick J.; Bennun, Sandra V; Andersen, Mikael Rørdam

    2017-01-01

    The Chinese hamster ovary (CHO) cell is the gold standard for manufacturing of glycosylated recombinant proteins for production of biotherapeutics. The similarity of its glycosylation patterns to the human versions enable the products of this cell line favorable pharmacokinetic properties and lower...

  4. O-GLYCOBASE version 4.0: a revised database of O-glycosylated proteins

    DEFF Research Database (Denmark)

    Gupta, Ramneek; Birch, Hanne; Rapacki, Krzysztof

    1999-01-01

    O-GLYCBASE is a database of glycoproteins with O-linked glycosylation sites. Entries with at least one experimentally verified O-glycosylation site have been complied from protein sequence databases and literature. Each entry contains information about the glycan involved, the species, sequence, ...

  5. A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolism.

    NARCIS (Netherlands)

    Morava, E.; Wevers, R.A.; Cantagrel, V.; Hoefsloot, L.H.; Al-Gazali, L.; Schoots, J.; Rooij, A. van; Huijben, K.; Ravenswaaij-Arts, C.M.A. van; Jongmans, M.C.J.; Sykut-Cegielska, J.; Hoffmann, G.F.; Bluemel, P.; Adamowicz, M.; Reeuwijk, J. van; Ng, B.G.; Bergman, J.E.; Bokhoven, J.H.L.M. van; Korner, C.; Babovic-Vuksanovic, D.; Willemsen, M.A.A.P.; Gleeson, J.G.; Lehle, L.; Brouwer, A.P.M. de; Lefeber, D.J.

    2010-01-01

    Cerebellar hypoplasia and slowly progressive ophthalmological symptoms are common features in patients with congenital disorders of glycosylation type I. In a group of patients with congenital disorders of glycosylation type I with unknown aetiology, we have previously described a distinct phenotype

  6. Low Density Lipoprotein Receptor Class A Repeats Are O-Glycosylated in Linker Regions

    DEFF Research Database (Denmark)

    Pedersen, Nis Borbye; Wang, Shengjun; Narimatsu, Yoshiki

    2014-01-01

    , which in wild-type CHO cells is glycosylated with the typical sialylated core 1 structure. The glycosites in linker regions of LDLR class A repeats are conserved in LDLR from man to Xenopus and found in other homologous receptors. O-Glycosylation is controlled by a large family of polypeptide Gal...

  7. O-GLYCBASE version 3.0: a revised database of O-glycosylated proteins

    DEFF Research Database (Denmark)

    Hansen, Jan; Lund, Ole; Nilsson, Jette

    1998-01-01

    O-GLYCBASE is a revised database of information on glycoproteins and their O-linked glycosylation sites. Entries are compiled and revised from the literature, and from the sequence databases. Entries include informations about species, sequence, glycosylation sites and glycan type and is fully cr...

  8. Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites

    DEFF Research Database (Denmark)

    Julenius, Karin; Mølgaard, Anne; Gupta, Ramneek

    2005-01-01

    could be predicted from averaged properties together with the fact that glycosylation sites are not precisely conserved indicates that mucin-type glycosylation in most cases is a bulk property and not a very site-specific one. NetOGlyc 3.1 is made available at www.cbs.dtu.dk/services/netoglyc....

  9. Oxytocin analogues with O-glycosylated serine and threonine in position 4

    Czech Academy of Sciences Publication Activity Database

    Marcinkowska, A.; Borovičková, Lenka; Slaninová, Jiřina; Grzonka, Z.

    2007-01-01

    Roč. 81, č. 7 (2007), s. 1335-1344 ISSN 0137- 5083 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z90210515 Keywords : oxytocin * glycosylated serin * glycosylated threonin * position 4 Subject RIV: CE - Biochemistry Impact factor: 0.483, year: 2007

  10. N-glycosylation by N-acetylglucosaminyltransferase V enhances the interaction of CD147/basigin with integrin β1 and promotes HCC metastasis.

    Science.gov (United States)

    Cui, Jian; Huang, Wan; Wu, Bo; Jin, Jin; Jing, Lin; Shi, Wen-Pu; Liu, Zhen-Yu; Yuan, Lin; Luo, Dan; Li, Ling; Chen, Zhi-Nan; Jiang, Jian-Li

    2018-05-01

    While the importance of protein N-glycosylation in cancer cell migration is well appreciated, the precise mechanisms by which N-acetylglucosaminyltransferase V (GnT-V) regulates cancer processes remain largely unknown. In the current study, we report that GnT-V-mediated N-glycosylation of CD147/basigin, a tumor-associated glycoprotein that carries β1,6-N-acetylglucosamine (β1,6-GlcNAc) glycans, is upregulated during TGF-β1-induced epithelial-to-mesenchymal transition (EMT), which correlates with tumor metastasis in patients with hepatocellular carcinoma (HCC). Interruption of β1,6-GlcNAc glycan modification of CD147/basigin decreased matrix metalloproteinase (MMP) expression in HCC cell lines and affected the interaction of CD147/basigin with integrin β1. These results reveal that β1,6-branched glycans modulate the biological function of CD147/basigin in HCC metastasis. Moreover, we showed that the PI3K/Akt pathway regulates GnT-V expression and that inhibition of GnT-V-mediated N-glycosylation suppressed PI3K signaling. In summary, β1,6-branched N-glycosylation affects the biological function of CD147/basigin and these findings provide a novel approach for the development of therapeutic strategies targeting metastasis. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  11. Concordance with World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines for cancer prevention and obesity-related cancer risk in the Framingham Offspring cohort (1991-2008).

    Science.gov (United States)

    Makarem, Nour; Lin, Yong; Bandera, Elisa V; Jacques, Paul F; Parekh, Niyati

    2015-02-01

    This prospective cohort study evaluates associations between healthful behaviors consistent with WCRF/AICR cancer prevention guidelines and obesity-related cancer risk, as a third of cancers are estimated to be preventable. The study sample consisted of adults from the Framingham Offspring cohort (n = 2,983). From 1991 to 2008, 480 incident doctor-diagnosed obesity-related cancers were identified. Data on diet, measured by a food frequency questionnaire, anthropometric measures, and self-reported physical activity, collected in 1991 was used to construct a 7-component score based on recommendations for body fatness, physical activity, foods that promote weight gain, plant foods, animal foods, alcohol, and food preservation, processing, and preparation. Multivariable Cox regression models were used to estimate associations between the computed score, its components, and subcomponents in relation to obesity-related cancer risk. The overall score was not associated with obesity-related cancer risk after adjusting for age, sex, smoking, energy, and preexisting conditions (HR 0.94, 95 % CI 0.86-1.02). When score components were evaluated separately, for every unit increment in the alcohol score, there was 29 % lower risk of obesity-related cancers (HR 0.71, 95 % CI 0.51-0.99) and 49-71 % reduced risk of breast, prostate, and colorectal cancers. Every unit increment in the subcomponent score for non-starchy plant foods (fruits, vegetables, and legumes) among participants who consume starchy vegetables was associated with 66 % reduced risk of colorectal cancer (HR 0.44, 95 % CI 0.22-0.88). Lower alcohol consumption and a plant-based diet consistent with the cancer prevention guidelines were associated with reduced risk of obesity-related cancers in this population.

  12. Asbestos-related occupational cancers compensated under the Industrial Accident Compensation Insurance in Korea.

    Science.gov (United States)

    Ahn, Yeon-Soon; Kang, Seong-Kyu

    2009-04-01

    Compensation for asbestos-related cancers occurring in occupationally-exposed workers is a global issue; this is also an issue in Korea. To provide basic information regarding compensation for workers exposed to asbestos, 60 cases of asbestos-related occupational lung cancer and mesothelioma that were compensated during 15 yr; from 1993 (the year the first case was compensated) to 2007 by the Korea Labor Welfare Corporation (KLWC) are described. The characteristics of the cases were analyzed using the KLWC electronic data and the epidemiologic investigation data conducted by the Occupational Safety and Health Research Institute (OSHRI) of the Korea Occupational Safety and Health Agency (KOSHA). The KLWC approved compensation for 41 cases of lung cancer and 19 cases of mesothelioma. Males accounted for 91.7% (55 cases) of the approved cases. The most common age group was 50-59 yr (45.0%). The mean duration of asbestos exposure for lung cancer and mesothelioma cases was 19.2 and 16.0 yr, respectively. The mean latency period for lung cancer and mesothelioma cases was 22.1 and 22.6 yr, respectively. The major industries associated with mesothelioma cases were shipbuilding and maintenance (4 cases) and manufacture of asbestos textiles (3 cases). The major industries associated with lung cancer cases were shipbuilding and maintenance (7 cases), construction (6 cases), and manufacture of basic metals (4 cases). The statistics pertaining to asbestos-related occupational cancers in Korea differ from other developed countries in that more cases of mesothelioma were compensated than lung cancer cases. Also, the mean latency period for disease onset was shorter than reported by existing epidemiologic studies; this discrepancy may be related to the short history of occupational asbestos use in Korea. Considering the current Korean use of asbestos, the number of compensated cases in Korea is expected to increase in the future but not as much as developed countries.

  13. Adjusting a cancer mortality-prediction model for disease status-related eligibility criteria

    Directory of Open Access Journals (Sweden)

    Kimmel Marek

    2011-05-01

    Full Text Available Abstract Background Volunteering participants in disease studies tend to be healthier than the general population partially due to specific enrollment criteria. Using modeling to accurately predict outcomes of cohort studies enrolling volunteers requires adjusting for the bias introduced in this way. Here we propose a new method to account for the effect of a specific form of healthy volunteer bias resulting from imposing disease status-related eligibility criteria, on disease-specific mortality, by explicitly modeling the length of the time interval between the moment when the subject becomes ineligible for the study, and the outcome. Methods Using survival time data from 1190 newly diagnosed lung cancer patients at MD Anderson Cancer Center, we model the time from clinical lung cancer diagnosis to death using an exponential distribution to approximate the length of this interval for a study where lung cancer death serves as the outcome. Incorporating this interval into our previously developed lung cancer risk model, we adjust for the effect of disease status-related eligibility criteria in predicting the number of lung cancer deaths in the control arm of CARET. The effect of the adjustment using the MD Anderson-derived approximation is compared to that based on SEER data. Results Using the adjustment developed in conjunction with our existing lung cancer model, we are able to accurately predict the number of lung cancer deaths observed in the control arm of CARET. Conclusions The resulting adjustment was accurate in predicting the lower rates of disease observed in the early years while still maintaining reasonable prediction ability in the later years of the trial. This method could be used to adjust for, or predict the duration and relative effect of any possible biases related to disease-specific eligibility criteria in modeling studies of volunteer-based cohorts.

  14. Validity and reproducibility of a food frequency questionnaire for dietary factors related to colorectal cancer

    OpenAIRE

    Tollosa, Daniel Nigusse; Van Camp, John; Huybrechts, Inge; Huybregts, Lieven; Van Loco, Joris; De Smet, Stefaan; Sterck, Ellen; Rabai, Celine; Van Hecke, Thomas; Vanhaecke, Lynn; Vossen, Els; Peeters, Marc; Lachat, Carl

    2017-01-01

    Abstract: Dietary factors play a major role in the development of colorectal cancer. This study evaluated the reproducibility and validity of a 109-food item Food Frequency Questionnaire (FFQ) to measure the consumption of foods and nutrients related to the development of colorectal cancer in a population aged 50 years in Flanders, Belgium. A semi-quantitative FFQ was administered two times in a period of two weeks to evaluate reproducibility (FFQ1 and FFQ2). The validity of the FFQ was asses...

  15. The approach of cancer related fatigue in rehabilitation medicine: Part II – Therapeutic interventions

    OpenAIRE

    Salca Amalia; Checiches Alexandra; Irsay Laszlo

    2015-01-01

    Starting with patient’ diagnose and continuing throughout the treatment and thereafter, cancer-related fatigue (CRF) is a distressing and disabling symptom, highly prevalent across the cancer continuum2. This is a review article mainly focusing on the rehabilitation objectives and interventions in CRF, and implementation issues, according to the report of an NCCN member institution4. Implementation is the most problematic, considering the large number of patients to whom it is addressed to...

  16. Heath-related quality of life in Spanish breast cancer patients: a systematic review

    OpenAIRE

    Delgado-Sanz, María Concepción; García-Mendizábal, María José; Pollán, Marina; Forjaz, Maria João; López-Abente, Gonzalo; Aragonés, Nuria; Pérez-Gómez, Beatriz

    2011-01-01

    Abstract Background Breast cancer is one of the oncological diseases in which health-related quality of life (HRQL) has been most studied. This is mainly due to its high incidence and survival. This paper seeks to: review published research into HRQL among women with breast cancer in Spain; analyse the characteristics of these studies; and describe the instruments used and main results reported. Methods The databases consulted were MEDLINE, EMBASE, PsycINFO, Dialnet, IBECS, CUIDEN, ISOC and L...

  17. Moderating effects of perceived growth on the association between fear of cancer recurrence and health-related quality of life among adolescent and young adult cancer survivors.

    Science.gov (United States)

    Cho, Dalnim; Park, Crystal L

    2017-01-01

    We examined whether (1) fear of cancer recurrence was related to lower health-related quality of life and (2) perceived growth moderated the link between fear of recurrence and health-related quality of life. About 292 adolescent and young adult cancer survivors (diagnosed with cancer at ages 15-34) completed a cross-sectional survey. Fear of recurrence was related to poorer physical and mental health-related quality of life. The negative association between fear of recurrence and mental health-related quality of life was moderated by perceived growth. Fostering perceived growth may mitigate the adverse associations of fear of recurrence and health-related quality of life.

  18. Antibody glycosylation and its impact on the pharmacokinetics and pharmacodynamics of monoclonal antibodies and Fc-fusion proteins.

    Science.gov (United States)

    Liu, Liming

    2015-06-01

    Understanding the impact of glycosylation and keeping a close control on glycosylation of product candidates are required for both novel and biosimilar monoclonal antibodies (mAbs) and Fc-fusion protein development to ensure proper safety and efficacy profiles. Most therapeutic mAbs are of IgG class and contain a glycosylation site in the Fc region at amino acid position 297 and, in some cases, in the Fab region. For Fc-fusion proteins, glycosylation also frequently occurs in the fusion partners. Depending on the expression host, glycosylation patterns in mAb or Fc-fusions can be significantly different, thus significantly impacting the pharmacokinetics (PK) and pharmacodynamics (PD) of mAbs. Glycans that have a major impact on PK and PD of mAb or Fc-fusion proteins include mannose, sialic acids, fucose (Fuc), and galactose (Gal). Mannosylated glycans can impact the PK of the molecule, leading to reduced exposure and potentially lower efficacy. The level of sialic acid, N-acetylneuraminic acid (NANA), can also have a significant impact on the PK of Fc-fusion molecules. Core Fuc in the glycan structure reduces IgG antibody binding to IgG Fc receptor IIIa relative to IgG lacking Fuc, resulting in decreased antibody-dependent cell-mediated cytotoxicity (ADCC) activities. Glycoengineered Chinese hamster ovary (CHO) expression systems can produce afucosylated mAbs that have increased ADCC activities. Terminal Gal in a mAb is important in the complement-dependent cytotoxicity (CDC) in that lower levels of Gal reduce CDC activity. Glycans can also have impacts on the safety of mAb. mAbs produced in murine myeloma cells such as NS0 and SP2/0 contain glycans such as Galα1-3Galβ1-4N-acetylglucosamine-R and N-glycolylneuraminic acid (NGNA) that are not naturally present in humans and can be immunogenic when used as therapeutics. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  19. TMEM199 Deficiency Is a Disorder of Golgi Homeostasis Characterized by Elevated Aminotransferases, Alkaline Phosphatase, and Cholesterol and Abnormal Glycosylation

    NARCIS (Netherlands)

    Jansen, Jos C.; Timal, Sharita; van Scherpenzeel, Monique; Michelakakis, Helen; Vicogne, Dorothée; Ashikov, Angel; Moraitou, Marina; Hoischen, Alexander; Huijben, Karin; Steenbergen, Gerry; van den Boogert, Marjolein A. W.; Porta, Francesco; Calvo, Pier Luigi; Mavrikou, Mersyni; Cenacchi, Giovanna; van den Bogaart, Geert; Salomon, Jody; Holleboom, Adriaan G.; Rodenburg, Richard J.; Drenth, Joost P. H.; Huynen, Martijn A.; Wevers, Ron A.; Morava, Eva; Foulquier, François; Veltman, Joris A.; Lefeber, Dirk J.

    2016-01-01

    Congenital disorders of glycosylation (CDGs) form a genetically and clinically heterogeneous group of diseases with aberrant protein glycosylation as a hallmark. A subgroup of CDGs can be attributed to disturbed Golgi homeostasis. However, identification of pathogenic variants is seriously

  20. Glycosylation of the N-terminal potential N-glycosylation sites in the human α1,3-fucosyltransferase V and -VI (hFucTV and -VI)

    DEFF Research Database (Denmark)

    Christensen, Lise Lotte; Bross, Peter Gerd; Ørntoft, Torben Falck

    2000-01-01

    Human alpha1,3-fucosyltransferase V and -VI (hFucTV and -VI) each contain four potential N-glycosylation sites (hFucTV: Asn60, Asn105, Asn167 and Asn198 and hFucTVI: Asn46, Asn91, Asn153 and Asn184). Glycosylation of the two N-terminal potential N-glycosylation sites (hFucTV: Asn60, Asn105 and h......FucTVI: Asn46 and Asn91) have never been studied in detail. In the present study, we have analysed the glycosylation of these potential N-glycosylation sites. Initially, we compared the molecular mass of hFucTV and -VI expressed in COS-7 cells treated with tunicamycin with the mass of the proteins...... in untreated cells. The difference in molecular mass between the proteins in treated and untreated cells corresponded to the presence of at least three N-linked glycans. We then made a series of mutants, in which the asparagine residues in the N-terminal potential N-glycosylation sites were replaced...

  1. Breast Cancer Survivors Report Similar Concerns Related to Return to Work in Developed and Developing Nations.

    Science.gov (United States)

    Luo, Shi-Xiang; Liu, Jun-E; Cheng, Andy S K; Xiao, Shu-Qin; Su, Ya-Li; Feuerstein, Michael

    2018-02-14

    Aim To determine whether breast cancer survivors (BCS) at work following the diagn