Identification of potential predictors and surrogates for the selection of patients who may benefit from the use of Racotumomab, as switch maintenance therapy, in patients with non-small cell lung cancer, stages IIIA, IIIB and IV.

Start Date09 Jul 2018

Sponsor / Collaborator

Center For Molecular Immunology

RPCEC00000206

/ SuspendedPhase 1

Open, single-center,clinical trial with racotumomab-alum vaccine in pediatric patients diagnosed with neuroblastoma, Ewing sarcoma or nephroblastoma.

Start Date20 Dec 2015

Sponsor / Collaborator

Center For Molecular Immunology

100 Clinical Results associated with GM3

100 Translational Medicine associated with GM3

0 Patents (Medical) associated with GM3

2,145

Literatures (Medical) associated with GM3

01 Feb 2025·Neurobiology of Disease

Elevation of ganglioside degradation pathway drives GM2 and GM3 within amyloid plaques in a transgenic mouse model of Alzheimer's disease

Article

Author: Whitehead, Shawn N ; Myers, Sarah J ; Ollen-Bittle, Nikita ; Wang, Wenxuan

Alzheimer's disease (AD) is a progressive neurodegenerative disease that accounts for two-thirds of all dementia cases, and age is the strongest risk factor. In addition to the amyloid hypothesis, lipid dysregulation is now recognized as a core component of AD pathology. Gangliosides are a class of membrane lipids of the glycosphingolipid family and are enriched in the central nervous system (CNS). Ganglioside dysregulation has been implicated in various neurodegenerative diseases, including AD, but the spatial distribution of ganglioside dysregulation with respect to amyloid-beta (Aβ) deposition is not well understood. To address this gap, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) was employed to investigate the age-dependent expression profiles of the A-series ganglioside species GD1a, GM1, GM2, and GM3 in the APP/PS1 transgenic mouse model of AD in which age-dependent amyloid-beta (Aβ) plaques develop. This study utilized a dual-resolution approach in combination with whole-brain imaging for comprehensive detection of ganglioside expression across neuroanatomical regions via high-resolution imaging of the cerebral cortex and hippocampus to investigate plaque-associated ganglioside alterations. The results revealed age-dependent changes in the complex gangliosides GM1 and GD1a across white and gray matter regions in both wildtype and APP/PS1 mice. Significantly greater levels of simple gangliosides GM2 and GM3 were observed in the cortex and dentate gyrus of the hippocampus in transgenic mice at 12 and 18 m than in age-matched controls. The accumulation of GM3 colocalized with Aβ plaques in aged APP/PS1 mice and correlated with Hexa gene expression, suggesting that ganglioside degradation is a mechanism for the accumulation of GM3. This work is the first to demonstrate that age-related ganglioside dysregulation is spatiotemporally associated with Aβ plaques using sophisticated MSI and reveals novel mechanistic insights into lipid regulation in AD.

01 Jan 2025·Advanced Science

Comprehensive Modular Synthesis of Ganglioside Glycans and Evaluation of their Binding Affinities to Siglec‐7 and Siglec‐9

Article

Author: Adak, Avijit K. ; Tseng, Hsin‐Kai ; Lyu, Ke‐Hong ; Lu, Wen ; Lin, Chun‐Cheng ; Chiang, Yu‐Ching ; Kuo, Wen‐Hua ; Lee, Yun‐Sheng ; Chang, Shu‐Yen ; Angata, Takashi

AbstractIn the present work, bacterial glycosyltransferases are utilized to construct ganglioside glycans in a convergent approach via a sugar‒nucleotide regeneration system and one‐pot multienzyme reactions. Starting from β‐lactoside enables the diversification of both the glycan moieties and the linkages in the lower α‐arm and upper β‐arm. Overall, a comprehensive panel of 24 natural a‐series (GM3, GM2, GM1a, GD1a, GT1a, and fucosyl‐GM1), b‐series (GD3, GD2, GD1b, GT1b, and GQ1b), c‐series (GT3, GT2, GT1c, GQ1c, and GP1c), α‐series (GM1α, GD1aα, and GT1aα), and o‐series (GA2, GA1, GM1b, GalNAc‐GM1b, and GD1c) ganglioside glycans are prepared, which are suitable for biological studies and further applications. Moreover, a microarray is constructed with these synthesized ganglioside glycans to investigate their binding specificity with recombinant Fc‐fused Siglec‐7 and Siglec‐9, which are immune checkpoint‐like glycan recognition proteins on natural killer cells. The microarray binding results reveal that GD3 and GT1aα are specific ligands for Siglec‐7 and Siglec‐9, respectively, and this discovery can lead to the identification of appropriate ligands for investigating the roles of these Siglecs in immunomodulation.

01 Nov 2024·Pigment Cell & Melanoma Research

ToF‐SIMS imaging reveals changes in tumor cell lipids during metastatic progression of melanoma

Article

Author: Zaar, Oscar ; Cehajic, Kevin Sjögren ; Bagge, Roger Olofsson ; Fletcher, John S. ; Katsarelias, Dimitrios ; Paoli, John ; Neittaanmäki, Noora ; Nilsson, Kelly Dimovska

AbstractMost melanomas progress from radial to vertical growth phase before spreading locoregionally and distally. Much is still unknown about the metabolic changes in the tumor cells and their microenvironment during this metastatic progression. We aimed to gain new insight into the molecular characteristics of melanoma in regard to spatial lipidomics to deliver new knowledge regarding tumor metastatic progression. We included 10 fresh tumor samples from 10 patients including two in situ melanomas, two invasive primary melanomas, and six metastatic melanomas (four in‐transit metastases and two distant metastases). In addition, we analyzed four healthy skin controls from the same patients. Time‐of‐flight imaging secondary ion mass spectrometry (ToF‐SIMS) enabled detailed spatial‐lipidomics that could be directly correlated with conventional histopathological analysis of consecutive H&E‐stained tissue sections. Significant differences in the lipid profiles were found in primary compared to metastatic melanomas, notably an increase in phosphatidylethanolamine lipids relative to phosphatidylinositol lipids and an increase in GM3 gangliosides in the metastatic samples. Furthermore, analysis of the data from in transit versus distant metastases samples highlighted that specific phospholipids, and a difference in the long versus shorter chain GM3 gangliosides, discriminated the metastatic routes. Further studies are warranted to verify these preliminary findings. Lipidomic changes could serve as a novel biomarker for tumor progression and even serve as a target for novel treatments. Furthermore, analyzing the lipid profiles could help to differentiate between primary and metastatic melanomas in challenging cases.

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