Multi-angle acquisition and 3D composite reconstruction for organ-targeted PET using planar detectors.

Background: This study investigates a multi-angle acquisition method aimed at improving image quality in organ-targeted PET detectors with planar detector heads. Organ-targeted PET technologies have emerged to address limitations of conventional whole-body PET/CT systems, such as restricted axial field-of-view (AFOV), limited spatial resolution, and high radiation exposure associated with PET procedures. The AFOV in organ-targeted PET can be adjusted to the organ of interest, minimizing unwanted signals from other parts of the body, thus improving signal collection efficiency and reducing the dose of administered radiotracer.

BCMA CAR-T induces complete and durable remission in refractory plasmablastic lymphoma.

Plasmablastic lymphoma (PBL) is a rare subtype of aggressive large B-cell lymphoma, with a dismal prognosis despite aggressive therapies. New approaches are needed for those with refractory disease. PBL expresses antigens similar to multiple myeloma (MM), including B-cell maturation antigen (BCMA).

Antitumor Activity against A549 Cancer Cells of Three Novel Complexes Supported by Coating with Silver Nanoparticles.

A novel biologically active organic ligand L (N'-benzylidenepyrazine-2-carbohydrazonamide) and its three coordination compounds have been synthesized and structurally described. Their physicochemical and biological properties have been thoroughly studied. Cu(II), Zn(II), and Cd(II) complexes have been analyzed by F-AAS spectrometry and elemental analysis.

Teclistamab is an active T cell-redirecting bispecific antibody against B-cell maturation antigen for multiple myeloma.

B-cell maturation antigen (BCMA), a member of the tumor necrosis factor family of receptors, is predominantly expressed on the surface of terminally differentiated B cells. BCMA is highly expressed on plasmablasts and plasma cells from multiple myeloma (MM) patient samples. We developed a BCMAxCD3 bispecific antibody (teclistamab [JNJ-64007957]) to recruit and activate T cells to kill BCMA-expressing MM cells.

A T-cell-redirecting bispecific G-protein-coupled receptor class 5 member D x CD3 antibody to treat multiple myeloma.

T-cell-mediated approaches have shown promise in myeloma treatment. However, there are currently a limited number of specific myeloma antigens that can be targeted, and multiple myeloma (MM) remains an incurable disease. G-protein-coupled receptor class 5 member D (GPRC5D) is expressed in MM and smoldering MM patient plasma cells.

First-in-Human Phase I Study of Aprutumab Ixadotin, a Fibroblast Growth Factor Receptor 2 Antibody-Drug Conjugate (BAY 1187982) in Patients with Advanced Cancer.

Background: Fibroblast growth factor receptor (FGFR) 2 is overexpressed in several tumor types, including triple-negative breast cancer and gastric cancer, both of which have a high unmet medical need. Aprutumab ixadotin (BAY 1187982) is the first antibody-drug conjugate (ADC) to target FGFR2 and the first to use a novel auristatin-based payload.

Objective: This first-in-human trial was conducted to determine the safety, tolerability, and maximum tolerated dose (MTD) of aprutumab ixadotin in patients with advanced solid tumors from cancer indications known to be FGFR2-positive.

[Lipid spectrum and function of kidneys before and after liver transplantation].

Background: In patients after liver transplantation cardiovascular complications is the third main reason of death afer allograf failure and infections. The most important factors in the development of cardiovascular diseases are dyslipidemia and impaired renal function. The aim of the study was to investigate the lipid spectrum and renal function in liver recipients in real clinical practice and the correspondence of their correction to current clinical recommendations for the diagnosis and treatment of dyslipidemia and chronic kidney disease (CKD).

[RESULTS OF DIAGNOSTICS AND TREATMENT OF ADRENOCORTICAL CANCER].

The results of examination and treatment of 96 patients with adrenocortical cancer (ACC) were analyzed. Local forms of ACC (I and II stages (T1-2N0M0) were found in 19 patients, locally advanced forms (III stage (T1-4NIM0; T3-4N0M0) - in 62 cases and metastatic forms of ACC (IV stage (TxNxM1) - in 15 patients. The diagnostic approach to ACC was optimized.

F-actin flow drives affinity maturation and spatial organization of LFA-1 at the immunological synapse.

Integrin-dependent interactions between T cells and antigen-presenting cells are vital for proper T cell activation, effector function, and memory. Regulation of integrin function occurs via conformational change, which modulates ligand affinity, and receptor clustering, which modulates valency. Here, we show that conformational intermediates of leukocyte functional antigen 1 (LFA-1) form a concentric array at the immunological synapse.

Coordinate control of cytoskeletal remodeling and calcium mobilization during T-cell activation.

Ca(2+) mobilization and cytoskeletal reorganization are key hallmarks of T-cell activation, and their interdependence has long been recognized. Recent advances in the field have elucidated the molecular pathways that underlie these events and have revealed several points of intersection. Ca(2+) signaling can be divided into two phases: initial events leading to release of Ca(2+) from endoplasmic reticulum stores, and a second phase involving STIM 1 (stromal interaction molecule 1) clustering and CRAC (calcium release activated calcium) channel activation.

Impaired presynaptic function and elimination of synapses at premature stages during postnatal development of the cerebellum in the absence of CALEB (CSPG5/neuroglycan C).

Chicken acidic leucine-rich EGF-like domain-containing brain protein (CALEB), also known as chondroitin sulfate proteoglycan (CSPG)5 or neuroglycan C, is a neural chondroitin sulfate-containing and epidermal growth factor (EGF)-domain-containing transmembrane protein that is implicated in synaptic maturation. Here, we studied the role of CALEB within the developing cerebellum. Adult CALEB-deficient mice displayed impaired motor coordination in Rota-Rod experiments.

F-actin polymerization and retrograde flow drive sustained PLCγ1 signaling during T cell activation.

Activation of T cells by antigen-presenting cells involves assembly of signaling molecules into dynamic microclusters (MCs) within a specialized membrane domain termed the immunological synapse (IS). Actin and myosin IIA localize to the IS, and depletion of F-actin abrogates MC movement and T cell activation. However, the mechanisms that coordinate actomyosin dynamics and T cell receptor signaling are poorly understood.

The cytoskeletal adaptor protein IQGAP1 regulates TCR-mediated signaling and filamentous actin dynamics.

The Ras GTPase-activating-like protein IQGAP1 is a multimodular scaffold that controls signaling and cytoskeletal regulation in fibroblasts and epithelial cells. However, the functional role of IQGAP1 in T cell development, activation, and cytoskeletal regulation has not been investigated. In this study, we show that IQGAP1 is dispensable for thymocyte development as well as microtubule organizing center polarization and cytolytic function in CD8(+) T cells.

Lymphocyte signaling converges on microtubules.

Movement of immunoreceptor microclusters tunes lymphocyte activation, but the underlying mechanisms are incompletely understood. In this issue of Immunity, Schnyder et al. (2011) and Hashimoto-Tane et al.

Impaired synapse function during postnatal development in the absence of CALEB, an EGF-like protein processed by neuronal activity.

In an attempt to characterize the molecular components by which electric activity influences the development of synapses, we searched for cell surface proteins modulated by calcium influx and glutamate receptor activity. Here, we report that neuronal depolarization facilitates the conversion of CALEB, which results in a truncated transmembrane form with an exposed EGF domain. To characterize the role of CALEB in synapse development, synaptic features were investigated in slices of the colliculus superior from CALEB-deficient mice.

Tumor necrosis by controlled ebullism.

In the early days of manned space flight, experiments were done in which dogs and chimpanzees were exposed to near vacuum in anticipation of possible manned space flight accidents. These specimens experienced what was termed "ebullism". This syndrome involved boiling of body fluids resulting in extreme dehydration and circulatory failure.

Platelet-derived growth factor activates production of reactive oxygen species by NAD(P)H oxidase in smooth muscle cells through Gi1,2.

Recent findings indicate that platelet-derived growth factor (PDGF) plays a role in the generation of reactive oxygen species (ROS) as second messengers in smooth muscle cells (SMC). To identify the source and signal transduction pathway of ROS formation in SMC, we investigated PDGF-induced ROS formation. Stimulation of SMC with PDGF resulted in a rapid increase of ROS production.

Molecular cloning of CoA Synthase. The missing link in CoA biosynthesis.

Coenzyme A functions as a carrier of acetyl and acyl groups in living cells and is essential for numerous biosynthetic, energy-yielding, and degradative metabolic pathways. There are five enzymatic steps in CoA biosynthesis. To date, molecular cloning of enzymes involved in the CoA biosynthetic pathway in mammals has been only reported for pantothenate kinase.

Phosphoinositide 3-kinase isoforms selectively couple receptors to vascular L-type Ca(2+) channels.

Heterodimeric class I phosphoinositide 3-kinase (PI3K) has been shown to be involved in the stimulation of voltage-gated Ca(2+) channels by various mediators. In this study, we bring evidences that vascular L-type Ca(2+) channels can be modulated by both tyrosine kinase-regulated class Ia and G protein-regulated class Ib PI3Ks. Purified recombinant PI3Ks increased the peak Ca(2+) channel current density when applied intracellularly.

Phosphoinositide 3-kinase gamma mediates angiotensin II-induced stimulation of L-type calcium channels in vascular myocytes.

Previous results have shown that in rat portal vein myocytes the betagamma dimer of the G(13) protein transduces the angiotensin II-induced stimulation of calcium channels and increase in intracellular Ca(2+) concentration through activation of phosphoinositide 3-kinase (PI3K). In the present work we determined which class I PI3K isoforms were involved in this regulation. Western blot analysis indicated that rat portal vein myocytes expressed only PI3Kalpha and PI3Kgamma and no other class I PI3K isoforms.

Gbeta 5gamma 2 is a highly selective activator of phospholipid-dependent enzymes.

In this study, Gbeta specificity in the regulation of Gbetagamma-sensitive phosphoinositide 3-kinases (PI3Ks) and phospholipase Cbeta (PLCbeta) isozymes was examined. Recombinant mammalian Gbeta(1-3)gamma(2) complexes purified from Sf9 membranes stimulated PI3Kgamma lipid kinase activity with similar potency (10-30 nm) and efficacy, whereas transducin Gbetagamma was less potent. Functionally active Gbeta(5)gamma(2) dimers were purified from Sf9 cell membranes following coexpression of Gbeta(5) and Ggamma(2-His).

Roles of non-catalytic subunits in gbetagamma-induced activation of class I phosphoinositide 3-kinase isoforms beta and gamma.

By using purified preparations we show that nanomolar concentrations of Gbetagamma significantly stimulated lipid kinase activity of phosphatidylinositol 3-kinase (PI3K) beta and PI3Kgamma in the presence as well as in the absence of non-catalytic subunits such as p85alpha or p101. Concomitantly, Gbetagamma stimulated autophosphorylation of the catalytic subunit of PI3Kgamma (EC(50), 30 nM; stoichiometry >/=0.6 mol of P(i)/mol of p110gamma), which also occurred in the absence of p101.