scholarly journals CIDP Antibodies Target Junction Proteins and Identify Patient Subgroups

2021 ◽  
Vol 8 (2) ◽  
pp. e944
Author(s):  
Christian P. Moritz ◽  
Yannick Tholance ◽  
Oda Stoevesandt ◽  
Karine Ferraud ◽  
Jean-Philippe Camdessanché ◽  
...  
Keyword(s):  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Age At Onset ◽  
Growth Factor Receptor ◽  
Principal Component ◽  
Immunoglobulin Therapy ◽  
Serum Samples ◽  
Younger Age ◽  
Specific Autoantibody ◽  
Epidermal Growth ◽  
Related Proteins

ObjectiveTo discover systemic characteristics in the repertoires of targeted autoantigens in chronic inflammatory demyelinating polyneuropathy (CIDP), we detected the entire autoantigen repertoire of patients and controls and analyzed them systematically.MethodsWe screened 43 human serum samples, of which 22 were from patients with CIDP, 12 from patients with other neuropathies, and 9 from healthy controls via HuProt Human Proteome microarrays testing about 16,000 distinct human bait proteins. Autoantigen repertoires were analyzed via bioinformatical autoantigenomic approaches: principal component analysis, analysis of the repertoire sizes in disease groups and clinical subgroups, and overrepresentation analyses using Gene Ontology and PantherDB.ResultsThe autoantigen repertoires enabled the identification of a subgroup of 10/22 patients with CIDP with a younger age at onset and a higher frequency of mixed motor and sensory CIDP. IV immunoglobulin therapy responders targeted 3 times more autoantigens than nonresponders. No CIDP-specific autoantibody is present in all patients; however, anchoring junction components were significantly targeted by 86.4% of patients with CIDP. There are potential novel CIDP-specific autoantigens such as the myelination- or axo-glial structure–related proteins actin-related protein 2/3 complex subunit 1B, band 4.1-like protein 2, cadherin-15, cytohesin-1, epidermal growth factor receptor, ezrin, and radixin.ConclusionsThe repertoire of targeted autoantigens of patients with CIDP differs in a systematic degree from those of controls. Systematic autoantigenomic approaches can help to understand the disease and to discover novel bioinformatical tools and novel autoantigen panels to improve diagnosis, treatment, prognosis, or patient stratification.

Epidermal growth factor receptor (EGFR) serum level may predict response in patients with advanced colorectal cancer (ACC) treated with gefitinib

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4119-4119 ◽  
Author(s):  
M. G. Zampino ◽  
E. Magni ◽  
L. Zorzino ◽  
L. Santoro ◽  
C. Massacesi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Progressive Disease ◽  
Advanced Colorectal Cancer ◽  
Objective Response ◽  
Surrogate Marker ◽  
Growth Factor Receptor ◽  
Binding Domain ◽  
Serum Samples ◽  
Cox's Regression ◽  
Epidermal Growth

4119 Background: EGFR-overexpression reported in colorectal cancer, justifies use of EGFR inhibitors. We conducted a phase II study (ESMO 2005) in ACC with the aim to assess efficacy of gefitinib plus oxaliplatin containing regimen. Main biological objective was to assess serum EGFR extra-cellular binding domain as surrogate marker of tyrosine-kinase inhibition and as predictor of outcome. Methods: 57 patients with EGFR-positive ACC,received gefitinib 250 mg/day combined with simplified FOLFOX-6 for at least 4 cycles,for a maximum of 10 courses.In not progressive disease, gefitinib was continued as maintenance treatment. Tumour assessment by RECIST criteria was performed at baseline and every 4 cycles.Serum EGFR extracellular binding-domain was evaluated by quantitative enzyme-linked immunoadsorbent.Serum EGFR as predictive factor was evaluated both taking into account the basal value only,and the whole EGFR pattern over time.The analyses were performed by logistic and Cox’s regression model with time-dependent covariate respectively;both models included centre, gender,age and site of primary tumours as adjusting factors. Results: Serum samples for EGFR were obtained at baseline and at every assessment.During mono-therapy phase the patients with serum samples decreased. Over treatment,34 patients reported a CR or PR as best objective response (BOR),while 9 patients showed SD or PD. Higher serum EGFR was associated to BOR both at baseline and over time.This result was confirmed by a similar analysis,which considered the whole EGFR profile,instead of the basal value only. Conclusions: Serum EGFR at baseline can be considered a significant predictor for the BOR.This observation is in line with data reported on lung cancer (Gregorc V, 2004).Although the EGFR trend over time seems to confirm the basal difference,this result should be taken with caution,due to the little number of cases reporting EGFR values besides the basal one. [Table: see text] No significant financial relationships to disclose.

Biosynthesis and glycosylation of the epidermal growth factor receptor in human tumor-derived cell lines A431 and Hep 3B

1986 ◽  
Vol 6 (1) ◽  
pp. 257-264
Author(s):  
C R Carlin ◽  
B B Knowles
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Lines ◽  
Related Species ◽  
Growth Factor Receptor ◽  
Human Tumor ◽  
Early Time ◽  
Charge Heterogeneity ◽  
Epidermal Growth ◽  
Related Proteins

Biosynthesis of the receptor for epidermal growth factor was investigated in two human tumor-derived cell lines, Hep 3B and A431. When grown in the presence of tunicamycin, both cells expressed a receptor-related species p135, the presumptive aglycosylated form of the biosynthetic precursor, gp145, of the mature form of the receptor, gp165, expressed at the cell surface. Two additional receptor-related species, p115 and p70, were detected when A431, but not Hep 3B, cells were treated with tunicamycin. Furthermore, digestion of the A431 receptor-related proteins with endoglycosidase F resulted in the detection of these three aglycosylated species. P70 appears to be the aglycosylated form of gp95, the presumptive intracellular precursor of the receptor-related species gp120 that is secreted by A431 but not Hep 3B cells; gp120 has a complex pattern of N-linked glycosylation, with consequent molecular weight and charge heterogeneity. P115 may be the aglycosylated form of a third biosynthetic intermediate, possibly a gp135 species detected in the early time points of pulse-chase labeling. Alternatively, p115 and gp135 may be derived co- or post-translationally by Ca2+-mediated proteolysis from p135 and gp145, respectively. The implications of the complexity of the biosynthesis of this molecule with regard to the multiple opportunities it affords the cell to modulate cell proliferation are discussed.

Multi-Target Drug Discovery Via PTML Modeling: Applications to the Design of Virtual Dual Inhibitors of CDK4 and HER2

2021 ◽  
Vol 21 ◽  
Author(s):  
Valeria V. Kleandrova ◽  
Marcus T. Scotti ◽  
Luciana Scotti ◽  
Alejandro Speck-Planche
Keyword(s):  
Inhibitory Activity ◽  
Growth Factor Receptor ◽  
Lipinski’S Rule ◽  
Target Drug ◽  
Oncology Research ◽  
Dual Inhibitors ◽  
Epidermal Growth ◽  
Lipinski’S Rule Of Five ◽  
Classification Prediction ◽  
Related Proteins

Background: Cyclin-dependent kinase 4 (CDK4) and the human epidermal growth factor receptor 2 (HER2) are two of the most promising targets in oncology research. Thus, a series of computational approaches have been applied to the search for more potent inhibitors of these cancer-related proteins. However, current approaches have focused on chemical analogs while predicting the inhibitory activity against only one of these targets, never against both. Aims: We report the first perturbation model combined with machine learning (PTML) to enable the design and prediction of dual inhibitors of CDK4 and HER2. Methods: Inhibition data for CDK4 and HER2 were extracted from ChEMBL. The PTML model relied on artificial neural networks to allow the classification/prediction of molecules as active or inactive against CDK4 and/or HER2. Results: The PTML model displayed sensitivity and specificity higher than 80% in the training set. The same statistical metrics had values above 75% in the test set. We extracted several molecular fragments and estimated their quantitative contributions to the inhibitory activity against CDK4 and HER2. Guided by the physicochemical and structural interpretations of the molecular descriptors in the PTML model, we designed six molecules by assembling several fragments with positive contributions. Three of these molecules were predicted as potent dual inhibitors of CDK4 and HER2, while the other three were predicted as inhibitors of at least one of these proteins. All the molecules complied with Lipinski’s rule of five and its variants. Conclusion: The present work represents an encouraging alternative for future anticancer chemotherapies.

scholarly journals Biosynthesis and glycosylation of the epidermal growth factor receptor in human tumor-derived cell lines A431 and Hep 3B.

1986 ◽  
Vol 6 (1) ◽  
pp. 257-264 ◽  
Author(s):  
C R Carlin ◽  
B B Knowles
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Lines ◽  
Related Species ◽  
Growth Factor Receptor ◽  
Human Tumor ◽  
Early Time ◽  
Charge Heterogeneity ◽  
Epidermal Growth ◽  
Related Proteins

Biosynthesis of the receptor for epidermal growth factor was investigated in two human tumor-derived cell lines, Hep 3B and A431. When grown in the presence of tunicamycin, both cells expressed a receptor-related species p135, the presumptive aglycosylated form of the biosynthetic precursor, gp145, of the mature form of the receptor, gp165, expressed at the cell surface. Two additional receptor-related species, p115 and p70, were detected when A431, but not Hep 3B, cells were treated with tunicamycin. Furthermore, digestion of the A431 receptor-related proteins with endoglycosidase F resulted in the detection of these three aglycosylated species. P70 appears to be the aglycosylated form of gp95, the presumptive intracellular precursor of the receptor-related species gp120 that is secreted by A431 but not Hep 3B cells; gp120 has a complex pattern of N-linked glycosylation, with consequent molecular weight and charge heterogeneity. P115 may be the aglycosylated form of a third biosynthetic intermediate, possibly a gp135 species detected in the early time points of pulse-chase labeling. Alternatively, p115 and gp135 may be derived co- or post-translationally by Ca2+-mediated proteolysis from p135 and gp145, respectively. The implications of the complexity of the biosynthesis of this molecule with regard to the multiple opportunities it affords the cell to modulate cell proliferation are discussed.

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