Protocol Considerations for In Vitro Metabolic Glycoengineering of Non-Natural Glycans.

Metabolic glycoengineering (MGE) refers to a technique where non-natural monosaccharide analogs are introduced into living biological systems. Once inside a cell, these compounds intercept a targeted biosynthetic glycosylation pathway and in turn are metabolically incorporated into cell-surface-displayed oligosaccharides, where they can modulate a host of biological activities or be exploited as tags for bioorthogonal and chemoselective ligation reactions. Over the past decade, azido-modified monosaccharides have become the go-to analogs for MGE; at the same time, analogs with novel chemical functionalities continue to be developed.

The European Paediatric Rare Tumours Network - European Registry (PARTNER) project for very rare tumors in children.

The PARTNER project (Paediatric Rare Tumours Network - European Registry) was launched in 2016. PARTNER aims to create a European Registry dedicated to children and adolescents with very rare tumors (VRT). It links existing national registries and provides a registry for those countries in which a VRT registry has not yet been created.

Nasopharyngeal carcinoma in children and adolescents: The EXPeRT/PARTNER diagnostic and therapeutic recommendations.

Nasopharyngeal carcinoma (NPC) is a rare pediatric tumor. Collaborative studies performed over the last decades showed improved results compared to historical data, but standardized guidelines for diagnosis and management of pediatric NPC are still unavailable. This study presents a European consensus guideline for the diagnosis and treatment of pediatric NPC developed by the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT).

Labeling glycans on living cells by a chemoenzymatic glycoengineering approach.

Structural glycobiology has traditionally been a challenging field due to a limited set of tools available to investigate the diverse and complex glycan molecules. However, we cannot ignore that glycans play critical roles in health as well as in disease, and are present in more than 50% of all proteins and on over 80% of all surface proteins. Chemoenzymatic glycoengineering (CGE) methods are a powerful set of tools to synthesize complex glycans, but the full potential of these methods have not been explored in cell biology yet.

Identification of sialylated glycoproteins from metabolically oligosaccharide engineered pancreatic cells.

In this study, we investigated the use of metabolic oligosaccharide engineering and bio-orthogonal ligation reactions combined with lectin microarray and mass spectrometry to analyze sialoglycoproteins in the SW1990 human pancreatic cancer line. Specifically, cells were treated with the azido N-acetylmannosamine analog, 1,3,4-Bu3ManNAz, to label sialoglycoproteins with azide-modified sialic acids. The metabolically labeled sialoglyproteins were then biotinylated via the Staudinger ligation, and sialoglycopeptides containing azido-sialic acid glycans were immobilized to a solid support.

Allergen sensitization linked to climate and age, not to intermittent-persistent rhinitis in a cross-sectional cohort study in the (sub)tropics.

Background: Allergen exposure leads to allergen sensitization in susceptible individuals and this might influence allergic rhinitis (AR) phenotype expression. We investigated whether sensitization patterns vary in a country with subtropical and tropical regions and if sensitization patterns relate to AR phenotypes or age.

Methods: In a national, cross-sectional study AR patients (2-70 y) seen by allergists underwent blinded skin prick testing with a panel of 18 allergens and completed a validated questionnaire on AR phenotypes.

Metabolic flux increases glycoprotein sialylation: implications for cell adhesion and cancer metastasis.

This study reports a global glycoproteomic analysis of pancreatic cancer cells that describes how flux through the sialic acid biosynthetic pathway selectively modulates a subset of N-glycosylation sites found within cellular proteins. These results provide evidence that sialoglycoprotein patterns are not determined exclusively by the transcription of biosynthetic enzymes or the availability of N-glycan sequons; instead, bulk metabolic flux through the sialic acid pathway has a remarkable ability to increase the abundance of certain sialoglycoproteins while having a minimal impact on others. Specifically, of 82 glycoproteins identified through a mass spectrometry and bioinformatics approach, ≈ 31% showed no change in sialylation, ≈ 29% exhibited a modest increase, whereas ≈ 40% experienced an increase of greater than twofold.

Metabolic oligosaccharide engineering with N-Acyl functionalized ManNAc analogs: cytotoxicity, metabolic flux, and glycan-display considerations.

Metabolic oligosaccharide engineering (MOE) is a maturing technology capable of modifying cell surface sugars in living cells and animals through the biosynthetic installation of non-natural monosaccharides into the glycocalyx. A particularly robust area of investigation involves the incorporation of azide functional groups onto the cell surface, which can then be further derivatized using "click chemistry." While considerable effort has gone into optimizing the reagents used for the azide ligation reactions, less optimization of the monosaccharide analogs used in the preceding metabolic incorporation steps has been done.

Metabolic oligosaccharide engineering: implications for selectin-mediated adhesion and leukocyte extravasation.

Metabolic oligosaccharide engineering is an emerging technology wherein non-natural monosaccharide analogs are exogenously supplied to living cells and are biosynthetically incorporated into cell surface glycans. A recently reported application of this methodology employs fluorinated analogs of ManNAc, GlcNAc, and GalNAc to modulate selectin-mediated adhesion associated with leukocyte extravasation and cancer cell metastasis. This monograph outlines possible mechanisms underlying the altered adhesion observed in analog-treated cells; these range from the most straightforward explanation (e.

Experimental Design Considerations for In Vitro Non-Natural Glycan Display via Metabolic Oligosaccharide Engineering.

Metabolic oligosaccharide engineering (MOE) refers to a technique where non-natural monosaccharide analogs are introduced into living biological systems. Once inside a cell, these compounds intercept a targeted biosynthetic glycosylation pathway and in turn are metabolically incorporated into cell-surface-displayed oligosaccharides where they can modulate a host of biological activities or be exploited as "tags" for bio-orthogonal and chemoselective ligation reactions. Undertaking a MOE experiment can be a daunting task based on the growing repertoire of analogs now available and the ever increasing number of metabolic pathways that can be targeted; therefore, a major emphasis of this article is to describe a general approach for analog design and selection and then provide protocols to ensure safe and efficacious analog usage by cells.

[Infantile vascular tumors].

The use in the past of an imprecise terminology to designate vascular tumors has contributed to its incorrect diagnosis, and as a consequence, to inadequate treatment. In childhood, different types of vascular tumors may be present. Hemangiomas of infancy are by far the most frequent, and other less common types are congenital hemangiomas (rapidly involuting or RICH and non-involuting or NICH), kaposiform hemangioendothelioma, angioblastoma or tufted angioma and pyogenic granuloma.

Radical surgery and IVA-chemotherapeutic regimen to treat embryonal rhabdomyosarcoma of the urachus: case report.

Although rhabdomyosarcoma is the most frequent soft tissue tumor in children, there are extremely few reports of this tumor arising from the urachus. The authors describe another case in a 6-year-old female associated with constipation and a painless suprapubic mass. The specimen had the pathological criteria used to define urachal sarcoma (cytological, histological, and immunohistochemical findings) and urachal remnants were not observed.

Internal mammary lymphadenopathy in breast carcinoma: CT appraisal of anatomic distribution.

Internal mammary lymph nodes are an important site of occult metastasis in clinically operable and recurrent breast carcinoma. Anatomic distribution of enlarged internal mammary nodes in patients with breast cancer was analyzed in a review of thoracic computed tomographic studies of 219 women with operable, advanced, or recurrent cancer. Enlarged nodes were observed in 45 patients (20.

Leiomyosarcoma of the penis. Case report and review of the literature.

The twenty-third case of penile leiomyosarcoma in the literature is reported, and all cases are reviewed. Clinically and pathologically these tumors fall into two groups, superficial and deep. Superficial tumors grow slowly, and tend to recur locally, but have a high salvage rate and good prognosis.

The effect of peripheral lymphoid cells on the incidence of lethal graft versus host disease following allogeneic mouse bone marrow transplantation.

Experiments were performed to study the role of circulating lymphoid cells in the incidence of lethal graft versus host disease (GVHD) in radiation-induced fully allogeneic mouse chimeras. The incidence of GVHD was reduced significantly in BALB/c leads to C57BL/6 radiation chimeras if bone marrow donors were exsanguinated immediately prior to marrow harvest. Chimeras resulting from the injection of bone marrow from bled donors exhibited only donor cells in spleen, bone marrow and peripheral blood and normal levels of Thy 1+ and Ia+ cells were found in each of these lymphoid compartments.