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Author(s):  
Ashraf Marzouk El Tantawi ◽  

proper S6K /BTK and PLCγ2 are main regulations for thromboxane-A synthesis, and necessary for B-cell maturations and T-cells modulations and functions. The main factors that cause the Osteoarthritis “OA” and diabetes and linked between them are the deficiency of Ser amino acids and decreasing or down regulations of Ser phosphorylation signalling pathway which necessary for proper S6K productions, where normally the Ser phosphorylation signalling pathway is the basis of Ser /Thr phosphorylation signalling which normally necessary for proper Akt, S6K1 synthesis and necessary for RORs and IFNs synthesis and also necessary for running proper BTK and proper PLCγ2 productions , where S6K is main regulator for ATPase and for proper PLCγ1 and for PLCγ2 synthesis which necessary for bone growth and for increasing and modulating immune efficiency


2022 ◽  
Vol 42 (2) ◽  
pp. 282-285
Author(s):  
Hongkyung Kim ◽  
Hye Min Kim ◽  
Jin Ju Kim ◽  
Saeam Shin ◽  
Doh Yu Hwang ◽  
...  

ESMO Open ◽  
2022 ◽  
Vol 7 (1) ◽  
pp. 100363
Author(s):  
S.F. Lee ◽  
B.A. Vellayappan ◽  
L.C. Wong ◽  
C.L. Chiang ◽  
S.K. Chan ◽  
...  

2022 ◽  
Author(s):  
Md. Alamgir Hossain ◽  
Kara Anasti ◽  
Brian Watts ◽  
Kenneth Cronin ◽  
Advaiti Pai Kane ◽  
...  

HIV-1 Envelope (Env) proteins designed to induce neutralizing antibody responses allow study of the role of affinities (equilibrium dissociation constant, KD) and kinetic rates (association/dissociation rates) on B cell antigen recognition. It is unclear whether affinity discrimination during B cell activation is based solely on Env protein binding KD, and whether B cells discriminate between proteins of similar affinities but that bind with different kinetic rates. Here we used a panel of Env proteins and Ramos B cell lines expressing IgM BCRs with specificity for CD4 binding-site broadly neutralizing (bnAb) or a precursor antibody to study the role of antigen binding kinetic rates on both early (proximal/distal signaling) and late events (BCR/antigen internalization) in B cell activation. Our results support a kinetic model for B cell activation in which Env protein affinity discrimination is based not on overall KD, but on sensing of association rate and a threshold antigen-BCR half-life.


Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 426
Author(s):  
Giuliana Beneduce ◽  
Antonia De Matteo ◽  
Pio Stellato ◽  
Anna M. Testi ◽  
Nicoletta Bertorello ◽  
...  

Five-year event-free survival in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) currently exceeds 80–85%. However, 15–20% of patients still experience a relapsed/refractory disease. From 1 January 2015 to 31 December 2020, thirty-nine patients, 0–21 years old with r/r BCP-ALL were treated with blinatumomab with the aim of inducing remission (n = 13) or reducing MRD levels (n = 26) in the frame of different multiagent chemotherapy schedules, in seven AIEOP centers. Patients were treated in compassionate and/or off-label settings and were not enrolled in any controlled clinical trials. Treatment was well tolerated; 22 (56.4%) patients reported adverse events (AE) on a total of 46 events registered, of which 27 (58.7%) were ≤2 grade according to CTCAE. Neurological AEs were 18 (39.1%); only two patients required transient blinatumomab discontinuation. Complete remission (CR) rate was 46% for the 13 patients treated with ≥5% blasts and 81% PCR/FC MRD negativity in the 26 patients with blasts < 5%. Median relapse-free survival was 33.4 months (95% CI; 7.5–59.3); median overall survival was not reached over a mean follow-up of 16 months. In our study, as in other real-life experiences, blinatumomab proved to be effective and well-tolerated, able to induce a high rate of CR and MRD negativity.


Healthcare ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 155
Author(s):  
Joaquim Carreras ◽  
Naoya Nakamura ◽  
Rifat Hamoudi

Mantle cell lymphoma (MCL) is a subtype of mature B-cell non-Hodgkin lymphoma characterized by a poor prognosis. First, we analyzed a series of 123 cases (GSE93291). An algorithm using multilayer perceptron artificial neural network, radial basis function, gene set enrichment analysis (GSEA), and conventional statistics, correlated 20,862 genes with 28 MCL prognostic genes for dimensionality reduction, to predict the patients’ overall survival and highlight new markers. As a result, 58 genes predicted survival with high accuracy (area under the curve = 0.9). Further reduction identified 10 genes: KIF18A, YBX3, PEMT, GCNA, and POGLUT3 that associated with a poor survival; and SELENOP, AMOTL2, IGFBP7, KCTD12, and ADGRG2 with a favorable survival. Correlation with the proliferation index (Ki67) was also made. Interestingly, these genes, which were related to cell cycle, apoptosis, and metabolism, also predicted the survival of diffuse large B-cell lymphoma (GSE10846, n = 414), and a pan-cancer series of The Cancer Genome Atlas (TCGA, n = 7289), which included the most relevant cancers (lung, breast, colorectal, prostate, stomach, liver, etcetera). Secondly, survival was predicted using 10 oncology panels (transcriptome, cancer progression and pathways, metabolic pathways, immuno-oncology, and host response), and TYMS was highlighted. Finally, using machine learning, C5 tree and Bayesian network had the highest accuracy for prediction and correlation with the LLMPP MCL35 proliferation assay and RGS1 was made. In conclusion, artificial intelligence analysis predicted the overall survival of MCL with high accuracy, and highlighted genes that predicted the survival of a large pan-cancer series.


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