CD40/Bp50 B-cell receptor has been implicated as having an important function for the regulation of human growth and maturation well antigen-driven selection tonsillar B-cells in germinal centers. The purpose present study was to examine biochemical events triggered by engagement CD40 B-lineage lymphoid cells corresponding discrete developmental stages ontogeny. on pro-B-, pre-pre-B-, pre-B-, or activated mature but not resting with agonistic anti-CD40 monoclonal antibody G28-5 resulted...

Ionizing radiation triggers a signal in human B-lymphocyte precursors that is intimately linked to an active protein-tyrosine kinase regulatory pathway. We show precursors, irradiation with gamma-rays leads (i) stimulation of phosphatidylinositol turnover; (ii) downstream activation by covalent modification multiple serine-specific protein kinases, including C; and (iii) nuclear factor kappa B. All the radiation-induced signals were effectively prevented inhibitors genistein herbimycin A....

We present evidence that the CD19 receptor is functionally operative and transmits pleiotropic signals throughout pro-B, pre-pre-B, pre-B, early B, mature B cell stages of human B-cell ontogeny. The signaling ability does not depend on existence a functional antigen complex (ARC). In precursors (BCP) lacking ARC, physically associated with Src family protein tyrosine kinases (PTK). engagement BCP high affinity anti-CD19 monoclonal antibody (mAb) or its homoconjugate rapidly activates PTK...

Functional interleukin 7 (IL-7) receptors are expressed on the surface of multiphenotypic, biphenotypic, and immature B-lineage human lymphoid precursor cells with germ-line immunoglobulin heavy-chain genes but not more mature rearranged and/or genes. Thus, IL-7 may have an important regulatory role during earliest stages B-cell ontogeny. The engagement recombinant (rhIL-7) results in enhanced tyrosine phosphorylation multiple phosphoproteins, stimulates inositol phospholipid turnover DNA...

ABSTRACT We have evaluated the clinical potential of TXU (anti-CD7)-pokeweed antiviral protein (PAP) immunoconjugate (TXU-PAP) as a new biotherapeutic anti-human immunodeficiency virus (anti-HIV) agent by evaluating its anti-HIV type 1 (anti-HIV-1) activity in vitro, well surrogate human peripheral blood lymphocyte-severe combined immunodeficient (Hu-PBL-SCID) mouse model AIDS. The present report documents side-by-side comparison superior vitro anti-HIV-1 TXU-PAP compared to activities...

The purposes of this study were to elucidate the effects recombinant human interleukin 7 (rhIL-7) on proliferation as well differentiation fetal thymocytes and analyze biochemical nature IL-7 receptor-linked transmembrane signal. In absence costimulants, rhIL-7 stimulated in vitro colony formation CD4+CD8+ double-positive immature thymocytes. Furthermore, promoted partial with a selective advantage for development CD4+CD8- single-positive Our observations suggest that likely has an important...

Here, we report that primary leukemic cells from infants with newly diagnosed B-precursor leukemia express a truncated and functionally defective CD22 coreceptor protein is unable to transmit apoptotic signals because it lacks most of the intracellular domain, including key regulatory signal transduction elements all cytoplasmic tyrosine residues. Expression this structurally abnormal associated very aggressive in vivo growth patients’ causing disseminated overt SCID mice. The encoded by...

Janus kinase 3 (JAK3), a member of the family protein-tyrosine kinases, is expressed in mast cells, and its enzymatic activity enhanced by IgE receptor/FcεRI cross-linking. Selective inhibition JAK3 cells with 4-(4′-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline) (WHI-P131) blocked phospholipase C activation, calcium mobilization, activation microtubule-associated protein after lgE Treatment IgE-sensitized rodent as well human WHI-P131 effectively inhibited activation-associated...

As presently reported, both ionizing radiation and engagement of the CD19 receptor are capable inducing apoptosis in B-lineage acute lymphoblastic leukemia (ALL) cells. In instances, activation tyrosine kinases appears to be a proximal mandatory step, since it can prevented by kinase inhibitor genistein. This common biochemical signaling pathway involves rapid Src family LCK (p56lck), which is physically associated with receptor, enhanced phosphorylation multiple substrates leading...

Here we present evidence that exposure of DT40 lymphoma B-cells to low energy electromagnetic fields (EMF) results in activation phospholipase C-γ 2 (PLC-γ2), leading increased inositol phospholipid turnover. PLC-γ2 EMF-stimulated cells is mediated by stimulation the Bruton's tyrosine kinase (BTK), a member Src-related TEC family protein kinases, which acts downstream LYN and upstream PLC-γ2. rendered BTK-deficient targeted disruption the<i>btk</i> gene did not show enhanced response EMF...

The quinazoline derivative 4-(4'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (WHI-P131/JANEX-1; CAS 202475-60-3) is a dual-function inhibitor of Janus kinase 3 (JAK3) and Epidermal Growth Factor (EGF) receptor kinase.A PEGylated liposomal nanoparticle formulation GMP-grade WHI-P131 exhibited potent in vivo activity against breast cancer cells.Notably, this therapeutic was substantially more effective than the standard chemotherapy drugs paclitaxel, gemcitabine, gefi tinib...

The t(1;19)(q23;p13) is one of the most common chromosomal translocations in acute lymphoblastic leukemia (ALL) and results production transforming oncoprotein E2A-PBX1. Here we first report a novel, biomarker-guided biotherapy strategy for personalized treatment t(1;19)(+) ALL. A supervised interrogation gene expression profiles primary leukemic cells from cohort 207 children with high risk B-lineage ALL identified up-regulated CD19 as biomarker disulfide-linked immunoconjugate...

Purpose: This study sought to investigate whether asprosin can be used in the diagnosis of GDM or for diagnostic purposes high-risk pregnancies, along with a review other parameters that may associated serum levels. Patients and Methods: The investigated association between gestational diabetes mellitus (GDM) A total 93 participants; 30 patients GDM, 33 healthy pregnant women normal glucose tolerance (NGT), non-diabetic (control group) at Endocrinology Metabolic Diseases outpatient clinic...

WHI-P131 (CAS 202475-60-3) is a dual-function inhibitor of JAK3 tyrosine kinase that demonstrated potent in vivo anti-inflammatory and anti-leukemic activity several preclinical animal models. This the first report development nanoparticle (NP) constructs ofWHI-P131. Fourty-eight distinct NP formulations were prepared encapsulation efficiencies > 95% intraliposomal concentrations >10 mg/mL achieved lead formulations. The anti-cancer WHI-P131-NP, PEGylated formulation was tested vitro vivo....

A novel spleen tyrosine kinase (SYK) P-site inhibitor, 1,4-Bis (9-O dihydroquinidinyl) phthalazine/hydroquinidine 1,4-phathalazinediyl diether (C-61), (but not vehicle) markedly enhanced H(2)O(2)-induced apoptosis of primary leukemia cells from each five relapsed B-lineage acute lymphoblastic (ALL) patients, as measured by in vitro TUNEL assays. highly radiation-resistant subclone the murine cell line BCL-1 was next used to investigate vivo radiosensitizing effects C-61. C-61 antileukemia...

The current study examined the chemopreventive potential of dual-function JAK3/EGFR tyrosine kinase inhibitor WHI-P131 (CAS 202475-60-3) in photocarcinogenesis non-melanoma skin cancer (NMSC). Prophylactic exhibited significant anti-inflammatory activity SKH-1 mouse model sunburn and afforded protection against inflammatory damage that results from UVB exposure. exposure (400 mJ/cm²) increased mutation rate transgene target UVB-exposed BigBlue mice by a factor 3.7 8.6 _×...