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SEOM Clinical Guideline for bone metastases from solid tumours (2016).

Bone metastases are common in many advanced solid tumours, being breast, prostate, thyroid, lung, and renal cancer the most prevalent. Bone metastases can produce skeletal-related events (SREs), defined as pathological fracture, spinal cord compression, need of bone irradiation or need of bone surgery, and hypercalcaemia. Patients with bone metastases experience pain, functional impairment and have a negative impact on their quality of life. Several imaging techniques are available for diagnosis of this disease. Bone-targeted therapies include zoledronic acid, a potent biphosfonate, and denosu

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… Radium dichloride 223 emits alpha particles, with high energy but low penetration (<100 μm or a range of 2–10 cells of diameter), and acts in the microenvironment of bone metastases [ 51 ]. …

Stereoselective HPLC assay of TJ0711 enantiomers by precolumn derivatization with GITC using UV detection and its application in pharmacokinetics in rats.

This investigation describes a new precise, sensitive and accurate stereoselective RP-HPLC method for determination of the enantiomers of a novel alpha- and beta-receptor blocking agent, 1-[4-(2-methoxyethyl) phenoxy]-3-[[2-(2- methoxyphenoxy) ethyl]amino]-2-propanol (TJ0711), in rat plasma. GITC was used for precolumn derivatization of TJ0711 enantiomers. Enantiomeric resolution was achieved on a Eurospher-100 C18 column (250 mm x 4.6 mm ID, 5-mum particle size), with UV detection at 255 nm, and the mobile phase consisted of acetonitrile and water (58:42, v/v) containing 0.02% glacial acetic

PrP glycoforms are associated in a strain-specific ratio in native PrPSc.

Prion diseases involve conversion of host-encoded cellular prion protein (PrPC) to a disease-related isoform (PrPSc). Using recombinant human beta-PrP, a panel of monoclonal antibodies was produced that efficiently immunoprecipitated native PrPSc and recognized epitopes between residues 93-105, indicating for the first time that this region is exposed in both human vCJD and mouse RML prions. In contrast, monoclonal antibodies raised to human alpha-PrP were more efficient in immunoprecipitating PrPC than PrPSc, and some of them could also distinguish between different PrP glycoforms. Using thes

Prion protein PrPc interacts with molecular chaperones of the Hsp60 family.

Prions mediate the pathogenesis of certain neurodegenerative diseases, including bovine spongiform encephalopathy in cattle and Creutzfeldt-Jakob disease in humans. The prion particle consists mainly, if not entirely, of PrPSc, a posttranslationally modified isoform of the cellular host-encoded prion protein (PrPc). It has been suggested that additional cellular factors might be involved in the physiological function of PrPc and in the propagation of PrPSc. Here we employ a Saccharomyces cerevisiae two-hybrid screen to search for proteins which interact specifically with the Syrian golden hams

Pickering emulsion as an oral delivery platform of anti-TNF-α antibody for ulcerative colitis therapy.

Monoclonal antibodies that block pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) are effective therapy for inflammatory bowel diseases (IBD). However, intravenous infusion (IV), the standard route of administration of anti-TNF-α monoclonal antibodies (TNF-Ab), is time-consuming and inconvenient for patients. Recently, subcutaneously administered TNF-Ab formulations were developed for at-home injections of maintenance doses, but self-injection using needle-based pen systems can lead to low patient compliance. Therefore, an oral TNF-Ab formulation could significantly increase the m

Sodium hyaluronate/lysine nanoparticles loaded with si-VEGF-A inhibits corneal neovascularization.

OBJECTIVE: This study designed sodium hyaluronate/lysine (SH/Lys)-based nanoparticles loaded with vascular endothelial growth factor A (VEGF-A) siRNA (V-SH/Lys), aiming to effectively treat corneal neovascularization (CNV) by specifically inhibiting the expression of VEGF-A. METHODS: The particle size, zeta potential and stability of the V-SH/Lys nanoparticles loaded with si-VEGF-A were tested. The effects of V-SH/Lys nanoparticles on the tube formation and migration of vascular endothelial cells were evaluated through Transwell, cell scratch assay and cell tube formation assay. A rat model o

Preclinical Efficacy of a PSMA-Targeted Thorium-227 Conjugate (PSMA-TTC), a Targeted Alpha Therapy for Prostate Cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA) is an attractive target for radionuclide therapy of metastatic castration-resistant prostate cancer (mCRPC). PSMA-targeted alpha therapy (TAT) has shown early signs of activity in patients with prostate cancer refractory to beta radiation. We describe a novel, antibody-based TAT, the PSMA-targeted thorium-227 conjugate PSMA-TTC (BAY 2315497) consisting of the alpha-particle emitter thorium-227 complexed by a 3,2-HOPO chelator covalently linked to a fully human PSMA-targeting antibody. EXPERIMENTAL DESIGN: PSMA-TTC was characterized for affini

Deletion of central alpha-helices in human apolipoprotein A-I: effect on phospholipid association.

In order to better understand the structure-function properties of apolipoprotein (apo) A-I, we have constructed and expressed three apoA-I mutants using a system previously described for the expression of human apolipoprotein A-I (Rec.-apoA-I). These mutants (corresponding to deletion of apoA-I residues 100-143, 122-165, 144-186) have been studied for their ability to form reconstituted apoA-I-containing lipoproteins (LpA-I) with POPC and DMPC, and for their structural and physical properties. Rec.- and native apoA-I can form homogeneous discoidal Lp2A-I over a wide range of POPC/apoA-I ratio

Arterial-injection chemotherapy for hepatocellular carcinoma using monodispersed poppy-seed oil microdroplets containing fine aqueous vesicles of epirubicin. Initial medical application of a membrane-emulsification technique.

BACKGROUND: Iodized poppy-seed oil (IPSO) has a property of depositing itself selectively in the cells of hepatocellular carcinoma (HCC). A mixture of anticancer agents and IPSO has been used widely because IPSO accumulates in tumors, but its usefulness appears limited because the anticancer agents become separated easily from IPSO and do not remain in the tumor. The authors prepared a long term inseparable, water-in-oil-in-water emulsion (W/O/W) for use in arterial-injection therapy for patients with HCC and evaluated its clinical usefulness. METHODS: The W/O/W was prepared by a membrane-emu

Formulation, Characterization, and In Vitro Biological Evaluation of a Triple-Phytochemical Nano Delivery System for Colon Cancer Therapy-A Preliminary Feasibility Study.

Background/Objectives: Poor oral bioavailability and limited intestinal permeation restrict the clinical translation of phytochemicals for colorectal cancer (CRC) therapy. The present preliminary study explored the development of a nanoparticle-based combinatorial formulation of resveratrol (Resv), acetyl-11-keto-β-boswellic acid (AKBA), and quercetin (Quer), to improve intestinal permeation and anti-cancer efficacy. Methods: A triple phytochemical nano formulation (designated as 3X) was developed and evaluated for morphology, particle size, zeta potential, encapsulation efficiency, and in vit

Preclinical evaluation of [225Ac]Ac-DOTA-TATE for treatment of lung neuroendocrine neoplasms.

PURPOSE: There is significant interest in the development of targeted alpha-particle therapies (TATs) for treatment of solid tumors. The metal chelator-peptide conjugate, DOTA-TATE, loaded with the β-particle emitting radionuclide 177Lu ([177Lu]Lu-DOTA-TATE) is now standard care for neuroendocrine tumors that express the somatostatin receptor 2 (SSTR2) target. A recent clinical study demonstrated efficacy of the corresponding [225Ac]Ac-DOTA-TATE in patients that were refractory to [177Lu]Lu-DOTA-TATE. Herein, we report the radiosynthesis, toxicity, biodistribution (BD), radiation dosimetry (RD

Evolutionary landscape and collaborative networks of global theranostic research in nuclear medicine: a visual bibliometric analysis.

BACKGROUND: Theranostics, integrating diagnostic imaging with targeted radionuclide therapy, has become central to nuclear medicine, but its global research landscape and collaboration patterns remain incompletely mapped. OBJECTIVE: To characterize publication dynamics, cooperative networks, and emerging topics in theranostic research from 2006 to 2024. METHODS: Articles and reviews indexed in the Web of Science Core Collection were retrieved for bibliometric analysis. Excel, CiteSpace, VOSviewer, Scimago Graphica, ArcGIS, and the R package bibliometrix were used for quantitative analysis an

Green Synthesized Gold Nanoparticles Using Naringin and Naringenin: Characterization, Biological Activities, and Cytogenotoxicity.

Background/Objectives: The green synthesis of gold nanoparticles (AuNPs) using plant-derived flavonoids offers a sustainable alternative to traditional methods. This study aimed to synthesize, characterize, and evaluate the biological activities and cytogenotoxicity of AuNPs functionalized with naringin (NG) and its aglycone, naringenin (NGN). Methods: Synthesis was optimized by varying pH, HAuCl4 concentration, reagent ratios, temperature, and stirring time. The resulting AuNPs-NG and AuNPs-NGN were characterized via Ultraviolet-Visible (UV-Vis) Spectroscopy, Fourier-Transform Infrared (FTIR)

The alpha-gal syndrome: Understanding the role of tick bites, and the delays in severe anaphylaxis.

The presence of serum immunoglobulin E (IgE) antibodies to the oligosaccharide galactose-alpha-1,3-galactose (α-gal) was first recognized during the investigation of allergic reactions to the monoclonal antibody cetuximab. The availability of an assay for IgE to α-gal made it possible to show that the patients who reported delayed allergic reactions to meat also had IgE to α-gal. This syndrome of delayed reactions to meat in patients with IgE to an oligosaccharide that was present in nonprimate mammals represented a complete contrast to the other forms of food allergy. However, the realization

Plasma proteomic analysis reveals altered protein abundances in HIV/HBV co-infection individuals with HCC and with liver cirrhosis.

To develop a risk prediction model for hepatocellular carcinoma (HCC) by screening differentially expressed proteins (DEPs) in HIV/HBV coinfected patients with HCC and liver cirrhosis using proteomic techniques. DEPs were identified in plasma from HIV/HBV co-infected patients with HCC and liver cirrhosis using quantitative liquid chromatography-mass spectrometry (LC-MS). Mapping discovered proteins to the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) databases yielded annotation information for DEPs. Differential plasma apolipoprotein A-1(APOA1)

Macrophage colony-stimulating factor and interleukin-6 release by periprosthetic cells stimulates osteoclast formation and bone resorption.

Periprosthetic bone loss is an important contributory factor for aseptic loosening of total joint replacements. It has recently been shown that osteoclast precursor cells are present in the wear particle-associated macrophage infiltrate found in the membrane surrounding loose implants and that these cells are capable of differentiating into osteoclastic bone-resorbing cells. Long-term co-culture of arthroplasty-derived macrophages and the rat osteoblast-like cell line, UMR-106, in the presence of 1,25(OH)2D3 results in the formation of numerous multinucleated cells that are positive for tartra

Toll-like receptor 9-mediated protection of enterovirus 71 infection in mice is due to the release of danger-associated molecular patterns.

Enterovirus 71 (EV71), a positive-stranded RNA virus, is the major cause of hand, foot, and mouth disease (HFMD) with severe neurological symptoms. Antiviral type I interferon (alpha/beta interferon [IFN-α/β]) responses initiated from innate receptor signaling are inhibited by EV71-encoded proteases. It is less well understood whether EV71-induced apoptosis provides a signal to activate type I interferon responses as a host defensive mechanism. In this report, we found that EV71 alone cannot activate Toll-like receptor 9 (TLR9) signaling, but supernatant from EV71-infected cells is capable of

Kaposi's Sarcoma-Associated Herpesvirus Inhibitor of cGAS (KicGAS), Encoded by ORF52, Is an Abundant Tegument Protein and Is Required for Production of Infectious Progeny Viruses.

UNLABELLED: Although Kaposi's sarcoma-associated herpesvirus (KSHV) ORF52 (also known as KSHV inhibitor of cGAS [KicGAS]) has been detected in purified virions, the roles of this protein during KSHV replication have not been characterized. Using specific monoclonal antibodies, we revealed that ORF52 displays true late gene expression kinetics and confirmed its cytoplasmic localization in both transfected and KSHV-infected cells. We demonstrated that ORF52 comigrates with other known virion proteins following sucrose gradient centrifugation. We also determined that ORF52 resides inside the vira

Computational and experimental identification of keystone interactions in Ebola virus matrix protein VP40 dimer formation.

The Ebola virus (EBOV) is a lipid-enveloped virus with a negative sense RNA genome that can cause severe and often fatal viral hemorrhagic fever. The assembly and budding of EBOV is regulated by the matrix protein, VP40, which is a peripheral protein that associates with anionic lipids at the inner leaflet of the plasma membrane. VP40 is sufficient to form virus-like particles (VLPs) from cells, which are nearly indistinguishable from authentic virions. Due to the restrictions of studying EBOV in BSL-4 facilities, VP40 has served as a surrogate in cellular studies to examine the EBOV assembly

Correlation between cervical HPV DNA detection and HPV16 seroreactivity measured with L1-only and L1+L2 viral capsid antigens.

Introduction. Persistent human papillomavirus (HPV) type 16 infection is the main causal agent of cervical cancer. Most HPV infections clear spontaneously within 1-2 years. Although not all infected women develop detectable HPV antibodies, about 60-70 % seroconvert and retain their antibodies at low levels.Aim. We investigated if cervical HPV16 DNA positivity was associated with HPV16 seroreactivity measured with two different antigen formulations. We assessed if associations were influenced by co-infection with other HPV types and HPV16 viral load.Methodology. We used baseline data for women