A5026978649- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Radiopharmaceutical Chemistry and Applications
- Cancer Cells and Metastasis
- Protein Degradation and Inhibitors
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Histone Deacetylase Inhibitors Research
- Nanoplatforms for cancer theranostics
- Cell Adhesion Molecules Research
- Medical Imaging Techniques and Applications
- Photodynamic Therapy Research Studies
- Bone health and treatments
- Nanoparticle-Based Drug Delivery
- Telomeres, Telomerase, and Senescence
- Cancer, Hypoxia, and Metabolism
- Medical Imaging and Pathology Studies
- Immunotherapy and Immune Responses
- Photoacoustic and Ultrasonic Imaging
- Optical Imaging and Spectroscopy Techniques
- Cancer therapeutics and mechanisms
- Drug Transport and Resistance Mechanisms
- CAR-T cell therapy research
- Advanced biosensing and bioanalysis techniques
- Cancer Immunotherapy and Biomarkers
Washington University in St. Louis
2016-2025
Mallinckrodt (United States)
2009-2024
Jewish Hospital
2019-2024
Barnes-Jewish Hospital
2019-2024
Alvin J. Siteman Cancer Center
2019-2024
Optica
2021
University of Missouri–St. Louis
2020
University of Washington
2005-2006
Molecular imaging has evolved over the past several years into an important tool for diagnosing, understanding, and monitoring disease. distinguished itself as interdisciplinary field, with contributions from chemistry, biology, physics, medicine. The cross-disciplinary impetus led to significant achievements, such development of more sensitive instruments robust, safer radiopharmaceuticals, thereby providing choices fit personalized medical needs. is making steadfast progress in field...
A biodegradable positron-emitting dendritic nanoprobe targeted at α v β 3 integrin, a biological marker known to modulate angiogenesis, was developed for the noninvasive imaging of angiogenesis. The has modular multivalent core-shell architecture consisting heterobifunctional core chemoselectively functionalized with polyethylene oxide (PEO) chains that form protective shell, which imparts stealth and dictates pharmacokinetics. Each 8 branches labeling radiohalogens. Placement radioactive...
A series of multivalent, functional polymer nanoparticles with diagnostic/imaging units and targeting ligands for molecular were synthesized the loading chain-end-functionalized GRGDS peptide sequence (model system based on integrin αvβ3) ranging from 0 to 50%. Accurate structural group control in these systems was achieved through a modular approach involving use multiple functionalized macromonomer/monomer combined living free radical polymerization. In cellulo results show an increase...
Abstract Most cancer patients succumb to disseminated disease because conventional systemic therapies lack spatiotemporal control of their toxic effects in vivo, particularly a complicated milieu such as bone marrow where progenitor stem cells reside. Here, we demonstrate the treatment by photoactivatable drugs using radiopharmaceuticals. An orthogonal-targeting strategy and contact-facilitated nanomicelle technology enabled highly selective delivery co-localization titanocene radiolabelled...
Multiple myeloma (MM) is a plasma B-cell hematologic cancer that causes significant skeletal morbidity. Despite improvements in survival, heterogeneity response remains major challenge MM. Cluster of differentiation 38 (CD38) type II transmembrane glycoprotein overexpressed cells and implicated MM cell signaling. Daratumumab U.S. Food Drug Administration–approved high-affinity monoclonal antibody targeting CD38 clinically benefiting refractory patients. Here, we evaluated...
Multiple myeloma (MM) is the cancer of plasma cells within bone marrow and remains incurable. Tumor-associated macrophages (TAMs) tumor microenvironment often display a pro-tumor phenotype correlate with proliferation, survival, therapy resistance. IL-10 key immunosuppressive cytokine that leads to recruitment development TAMs. In this study, we investigated role in MM TAM as well therapeutic application IL-10/IL-10R/STAT3 signaling inhibition. We demonstrated overexpressed BM mediates...
Very-late-antigen-4 (VLA-4, α<sub>4</sub>β<sub>1</sub> integrin, CD49d/CD29) is a transmembrane adhesion receptor that plays an important role in cancer and immune responses. Enhanced VLA-4 expression has been observed multiple myeloma (MM) cells surrounding stroma. conformational activation associated with MM pathogenesis. promising imaging therapeutic biomarker. <b>Methods:</b> Specificity of <sup>64</sup>Cu-LLP2A (<sup>64</sup>Cu-CB-TE1A1P-PEG<sub>4</sub>-LLP2A), high-affinity...
Biomedical imaging techniques such as skeletal survey and 18F-fluorodeoxyglucose (FDG)/Positron Emission Tomography (PET) are frequently used to diagnose stage multiple myeloma (MM) patients. However, has limited sensitivity it can detect osteolytic lesions only after 30–50% cortical bone destruction, FDG is a marker of cell metabolism that for intramedullary in MM. Targeted, non-invasive novel probes needed sensitively selectively image the unique molecular signatures cellular processes...
Rapid liver and spleen opsonization of systemically administered nanoparticles (NPs) for in vivo applications remains the Achilles' heel nanomedicine, allowing only a small fraction materials to reach intended target tissue. Although focusing on diseases that reside natural disposal organs is viable option, it limits plurality lesions could benefit from nanomedical interventions. Here we designed theranostic nanoplatform consisting reactive oxygen (ROS)-generating titanium dioxide (TiO2)...
There remains an unmet need for molecularly targeted imaging agents multiple myeloma (MM). The integrin very late antigen 4 (VLA4), is differentially expressed in malignant MM cells and pathogenic inflammatory microenvironmental cells. [
Abstract Purpose Multiple myeloma (MM) affects over 35,000 patients each year in the US. There remains a need for versatile Positron Emission Tomography (PET) tracers detection, accurate staging, and monitoring of treatment response MM that have optimal specificity translational attributes. CD38 is uniformly overexpressed thus represents an ideal target to develop CD38-targeted small molecule PET radiopharmaceuticals address these challenges. Procedures Using phage display peptide libraries...
Despite advances in cancer treatment over the past few decades, metastatic disease remains primary cause of morbidity and mortality. Recent reports suggest formation a "premetastatic niche" before cascade, where <i>niche</i> is defined as microenvironment for tumor cells to be able engraft proliferate at secondary sites. Bone marrow–derived (BMD) that express vascular endothelial growth factor receptor–1 very late antigen–4 (VLA-4) have been shown arrive sites metastasis form receptive...
Metastatic breast cancer is an intractable disease that responds poorly to immunotherapy. We show p38MAPKα inhibition (p38i) limits tumor growth by reprogramming the metastatic microenvironment in a CD4+ T cell-, IFNγ-, and macrophage-dependent manner. To identify targets further increased p38i efficacy, we utilized stromal labeling approach single-cell RNA sequencing. Thus, combined OX40 agonist synergistically reduced overall survival. Intriguingly, patients with signature had better...
Nanoparticles have been assessed in preclinical models of atherosclerosis for detection plaque complexity and treatment. However, their successful clinical translation has hampered by less than satisfactory lack a general strategy assessing the translational potential nanoparticles. Herein, nanoparticles based on comb-co-polymer assemblies were synthesized through modular construction approach with precise control over conjugation multiple functional building blocks vivo evaluation. This...
Multiple myeloma (MM) is a cancer of bone marrow (BM) plasma cells, which increasingly treatable but still incurable. In 90% MM patients, severe osteolysis results from pathological interactions between cells and the microenvironment. Delineating specific molecules pathways for their role in supportive BM vital developing new therapies. Very Late Antigen 4 (VLA4, integrin α4β1) key player cell-cell adhesion signaling cells. We evaluated VLA4 selective near infrared fluorescent probe,...
We hypothesized that in multiple myeloma cells (MMC), high membrane biosynthesis will induce acetate uptake vitro and vivo Here, we studied metabolism targeting MMC tested the efficacy of 11C-acetate-positron emission tomography (PET) to detect quantitatively image treatment response EXPERIMENTAL DESIGN: Acetate fate tracking using 13C-edited-1H NMR (nuclear magnetic resonance) was performed study MMC. Effects pharmacological modulation transport or incorporation into lipids on cell survival...
Treatment of the cationic iridathiabenzene (3) with sodium tert-butylthiolate leads to production a stable neutral iridathiabenzene, (4). Compound 4 exists in solution as an equilibrating mixture two square pyramidal isomers, "cis" 4a and "trans" 4b. When is cooled −30 °C acetonitrile, it precipitates acetonitrile adduct, (6), featuring iridathiacyclohexa-1,3-diene ring system. 6 reverts back upon redissolving warming room temperature. (or 6) excess PMe3 results addition iridium center...
The reactions of (Cl)Rh(PR3)3 (R = Me, Et) with the anionic thiapentadienide reagent lithium 2,3-dimethyl-5-thiapentadienide have been investigated. Treatment (Cl)Rh(PMe3)3 produces ((1,2,5-η)-2,3-dimethyl-5-thiapentadienyl)Rh(PMe3)3 (1), in which thiapentadienyl ligand is σ-bonded to rhodium through sulfur end chain and π-bonded carbon (C1−C2 double bond). In solution at room temperature, 1 undergoes a rapid dynamic process involving release recoordination bond C1−C2, causing two phosphine...