The Potential Role of Solvation in Antibody Recognition of the Lewis Y Antigen.

The Potential Role of Solvation in Antibody Recognition of the Lewis Y Antigen. Monoclon Antib Immunodiagn Immunother. 2015 Oct;34(5):295-302 Authors: Saha S, Murali R, Pashov A, Kieber-Emmons T Abstract Solvents play an important role in protein folding, protein-protein associations, stability, and specificity of recognition as in the case of antibody-antigen interactions through hydrogen bonds. One of the underappreciated features of protein-associated waters is that it weakens inter- and intra-molecular interactions by modulating electrostatic interactions and influencing conformational changes. Such observations demonstrate the direct relationship between macroscopic solvent effects on protein-protein interactions and atom-scale solvent-protein interactions. Although crystallographic solvents do explain some aspects of solvent-mediated interactions, molecular simulation allows the study of the dynamic role of solvents. Thus, analysis of conformations from molecular simulations are employed to understand the role of solvent on the inherent polyspecificity of a Lewis Y reactive germline gene relative to its expanded hybridomas and a humanized anti-Lewis Y antibody. Our analysis reveals that solvent mediates critical contacts through charged residues to facilitate cross-reactivity to carbohydrate antigens, but also increases the flexibility of some anti-Lewis Y antibodies concomitant with mutations (amino acid substitutions) to the germline antibody. Suc...
Source: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy - Category: Microbiology Tags: Monoclon Antib Immunodiagn Immunother Source Type: research

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This study estimated healthcare costs and utilisation for patients with AR and asthma. Mean annual outpatient visits, pharmaceutical costs and inpatient hospitalisations were calculated for 2010 and 2014, with pharmaceutical and inpatient costs stratified by AIT use. AR and asthma patients had a 35% higher mean number of physician visits and up to 90% higher mean pharmaceutical costs compared to controls. The cost of pharmaceuticals and inpatient hospitalisations were 54% lower in those prescribed AIT. Further research is recommended to understand the reasons for these cost differences. PMID: 31818082 [PubMed - as supplied by publisher]
Source: European Annals of Allergy and Clinical Immunology - Category: Allergy & Immunology Tags: Eur Ann Allergy Clin Immunol Source Type: research
The objective of the present review was to assess the most recent data, specifically addressing methods of risk stratification, duration of therapy, and future directions. Methods: PubMed and medline were searched for literature pertinent to adjuvant chemotherapy in either stage ii or stage iii colorectal cancer. Summary: Locoregional disease, histopathology, age, laterality, and a number of other biologic and molecular markers appear to have a role in disease risk stratification. The duration of adjuvant therapy for stage iii disease can vary based on risk factors, but use of adjuvant therapy and duration of thera...
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
Authors: Parmar A, Chan KKW, Ko YJ Abstract Therapeutic options for chemorefractory metastatic colorectal cancer (mcrc) have significantly expanded since 2009. The oral targeted therapies regorafenib and trifluridine/tipiracil have been established to be efficacious and safe in patients with mcrc who have progressed beyond 2 or more lines of chemotherapy. Evidence for the use of immunotherapy in a subgroup of this patient population is also encouraging, particularly in patients with mcrc that exhibits high microsatellite instability or deficient mismatch repair. Those significant advances have led to Health Canada ...
Source: Current Oncology - Category: Cancer & Oncology Tags: Curr Oncol Source Type: research
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Source: Best Practice and Research Clinical Endocrinology and Metabolism - Category: Endocrinology Source Type: research
Publication date: Available online 10 December 2019Source: Trends in Pharmacological SciencesAuthor(s): Yang Liu, Pan ZhengA major paradigm in cancer immunotherapy is the use of checkpoint inhibitors to break regulatory mechanisms that usually guard the host against autoimmune diseases. CTLA-4-targeting immunotherapy was the first example that helped establish this paradigm. However, the clinically tested anti-CTLA-4 antibodies exhibit suboptimal efficacy but high toxicity. Recent studies have demonstrated that immunotherapy-related adverse events (irAE) and the cancer immunotherapeutic effect (CITE) represent distinct and...
Source: Trends in Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research
Current practice in managing regional disease in head and neck melanoma is with a comprehensive neck dissection. The knowledge that this does not afford a survival benefit combined with recent encouraging advances in immunotherapy do raise the question if a lesser procedure such as a selective neck dissection (SND) would be more appropriate. We would like to invite discussion into the prospect of using this treatment in malignant cutaneous melanoma of the head and neck.
Source: Journal of Plastic, Reconstructive and Aesthetic Surgery - Category: Cosmetic Surgery Authors: Tags: Correspondence and Communications Source Type: research
Publication date: January 2020Source: Molecular Immunology, Volume 117Author(s): Bao-Hua Li, Malgorzata A. Garstka, Zong-Fang LiAbstractMyeloid-derived suppressor cells (MDSCs) expand in tumor-bearing host. They suppress anti-tumor immune response and promote tumor growth. Chemokines play a vital role in recruiting MDSCs into tumor tissue. They can also induce the generation of MDSCs in the bone marrow, maintain their suppressive activity, and promote their proliferation and differentiation. Here, we review CCL2/CCL12-CCR2, CCL3/4/5-CCR5, CCL15-CCR1, CX3CL1/CCL26-CX3CR1, CXCL5/2/1-CXCR2, CXCL8-CXCR1/2, CCL21-CCR7, CXCL13-C...
Source: Molecular Immunology - Category: Allergy & Immunology Source Type: research
Authors: Labrie M, Fang Y, Kendsersky ND, Li J, Liang H, Westin SN, Mitri Z, Mills GB Abstract Tumor cells and the tumor ecosystem rapidly evolve in response to therapy. This tumor evolution results in the rapid emergence of drug resistance that limits the magnitude and duration of response to therapy including chemotherapy, targeted therapy, and immunotherapy. Thus, there is an urgent need to understand and interdict tumor evolution to improve patient benefit to therapy. Reverse phase protein array (RPPA) provides a powerful tool to evaluate and develop approaches to target the processes underlying one form of tum...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Publication date: Available online 11 December 2019Source: Life SciencesAuthor(s): Rui Yan, JianJian Li, Ying Zhou, Li Yao, Ruya Sun, Ying Xu, Yang Ge, Guangyu AnAbstractImmunotherapy is one of the most promising strategies for cancer, compared with traditional treatments. As one of the key emerging immunotherapies, anti-PD-1/PD-L1 treatment has brought survival benefits to many advanced cancer patients. However, in pancreatic cancer, immunotherapy-based approaches have not achieved a favorable clinical effect because of mismatch repair deficiencies. Therefore, the majority of pancreatic tumors are regarded as immune-quies...
Source: Life Sciences - Category: Biology Source Type: research
(Yale University) In the last decade, scientists discovered that blocking a key regulator of the immune system helped unleash the body's natural defenses against several forms of cancer, opening up a new era of cancer immunotherapy. Now Yale scientists have essentially flipped this script and found that when impaired a molecularly similar regulator can cause the damaging immune system attacks on skin and organs that are the hallmark of the autoimmune disease lupus.
Source: EurekAlert! - Cancer - Category: Cancer & Oncology Source Type: news
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