The Sialome of the Retina, Alteration in Age-Related Macular Degeneration Pathology, and Potential Impacts on Complement Factor H.

Purpose: Little is known about sialic acids of the human retina, despite their integral role in self /non-self-discrimination by complement factor H (FH), the alternative complement pathway inhibitor.

Methods: A custom sialoglycan microarray was used to characterize the sialic acid-binding specificity of native FH or recombinant molecules where IgG Fc was fused to FH domains 16 to 20 (which contains a sialic acid-binding site), domains 6 and 7 (which contains a glycosaminoglycan-binding site), or the FH-related proteins (FHRs) 1 and 3. We analyzed macular and peripheral retinal tissue from postmortem ocular globes for the amount, type, and presentation (glycosidic linkage type) of sialic acid in individuals with age-related macular degeneration (AMD) and age-matched controls using fluorescent lectins and antibodies to detect sialic acid and endogenous FH.

N-Glycosylation as a Key Requirement for the Positive Interaction of Integrin and uPAR in Glioblastoma.

Integrin αV (IαV) and the urokinase-type plasminogen activator receptor (uPAR) are key mediators of tumor malignancy in Glioblastoma. This study aims to characterize IαV/uPAR interaction in GBM and investigate the role played by glycans in this scenario. Protein expression and interaction were confirmed via confocal microscopy and co-immunoprecipitation.

The sialome of the retina, alteration in age-related macular degeneration (AMD) pathology and potential impacts on Complement Factor H.

Purpose: Little is known about sialic acids of the human retina, despite their integral role in self/non-self-discrimination by complement factor H (CFH), the alternative complement pathway inhibitor.

Methods: A custom sialoglycan microarray was used to characterize the sialic acid-binding specificity of native CFH or recombinant molecules where IgG Fc was fused to CFH domains 16-20 (contains a sialic acid-binding site), domains 6-7 (contains a glycosaminoglycan-binding site) or the CFH-related proteins (CFHRs) 1 and 3. We analyzed macular and peripheral retinal tissue from post-mortem ocular globes for amount, type, and presentation (glycosidic linkage type) of sialic acid in individuals with age-related macular degeneration (AMD) and age-matched controls using fluorescent lectins and antibodies to detect sialic acid and endogenous CFH.

Human-specific elimination of epithelial Siglec-XII suppresses the risk of inflammation-driven colorectal cancers.

Carcinomas are common in humans but rare among closely related "great apes." Plausible explanations, including human-specific genomic alterations affecting the biology of sialic acids, are proposed, but causality remains unproven. Here, an integrated evolutionary genetics-phenome-transcriptome approach studied the role of SIGLEC12 gene (encoding Siglec-XII) in epithelial transformation and cancer.

Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma.

Gliomas are the most common intracranial primary tumors, for which very few therapeutic options are available. The most malignant subtype is the glioblastoma, a disease associated with a 5-year survival rate lower than 5%. Given that research in glycobiology continues highlighting the role of glycans in tumor cell biology, it offers an interesting niche for the search of new therapeutic targets.

Expression of bladder cancer-associated glycans in murine tumor cell lines.

The characterization of murine cell lines is of great importance in order to identify preclinical models that could resemble human diseases. Aberrant glycosylation includes the loss, excessive or novel expression of glycans and the appearance of truncated structures. MB49 and MB49-I are currently the only two murine cell lines available for the development of preclinical bladder cancer models.

Aberrant O-glycosylation modulates aggressiveness in neuroblastoma.

Neuroblastoma (NB) is the most common pediatric malignancy diagnosed before the first birthday in which MYCN oncogene amplification is associated with poor prognosis. Although aberrant glycosylation is an important actor in cell biology, little is known about its role in pediatric cancers such as NB. In this work we characterized the glycophenotype and the enzyme expression involved in glycans biosynthesis in five established human NB cell lines and in patient-derived primary tumors with different MYCN status.

Antibody-dependent cell-mediated cytotoxicity induced by active immunotherapy based on racotumomab in non-small cell lung cancer patients.

Antitumor strategies based on positive modulation of the immune system currently represent therapeutic options with prominent acceptance for cancer patients' treatment due to its selectivity and higher tolerance compared to chemotherapy. Racotumomab is an anti-idiotype (anti-Id) monoclonal antibody (mAb) directed to NeuGc-containing gangliosides such as NeuGcGM3, a widely reported tumor-specific neoantigen in many human cancers. Racotumomab has been approved in Latin American countries as an active immunotherapy for advanced non-small cell lung cancer (NSCLC) treatment.

Comparability of Antibody-Mediated Cell Killing Activity Between a Proposed Biosimilar RTXM83 and the Originator Rituximab.

Background: Biosimilars are described as biological products that resemble the structure of original biologic therapeutic products, with no clinically meaningful differences in terms of safety and effectiveness from the original. A wide range of biosimilars are under development or are already licensed in many countries. Biosimilars are earning acceptance and becoming a reality for immunotherapy treatments mainly based on the alternatives for the commercial anti-CD20 monoclonal antibody rituximab.