Searching for Protein Off-Targets of Prostate-Specific Membrane Antigen-Targeting Radioligands in the Salivary Glands.

Prostate specific membrane antigen (PSMA)-targeted radioligand therapies represent a highly effective treatment for metastatic prostate cancer. However, high and sustain uptake of PSMA-ligands in the salivary glands led to dose limiting dry mouth (xerostomia), especially with α-emitters. The expression of PSMA and histologic analysis couldn't directly explain the toxicity, suggesting a potential off-target mediator for uptake.

PET Imaging of Hepatocellular Carcinoma Using ZD2-(Ga-NOTA).

Purpose: We tested a recently developed short peptide radioligand for PET imaging of hepatocellular carcinoma (HCC) by targeting an oncoprotein, extra-domain B fibronectin (EDB-FN) in the tumor microenvironment.

Methods: The radioligand consists of a small linear peptide ZD2 with Ga-NOTA chelator, and specifically binds to EDB-FN. PET images were acquired dynamically for 1 hour after intravenously (i.

Imaging of Tumor-Associated Vascular Prostate-Specific Membrane Antigen in Woodchuck Model of Hepatocellular Carcinoma.

Background And Aims: Radiolabeled short peptide ligands targeting prostate-specific membrane antigen (PSMA) were developed initially for imaging and treatment of prostate cancers. While many nonprostate solid tumors including hepatocellular carcinoma (HCC) express little PSMA, their neovasculature expresses a high level of PSMA, which is avid for Gallium-68-labeled PSMA-targeting radio-ligand (Ga-PSMA-11) for positron emission tomography (PET). However, the lack of a spontaneous animal model of tumor-associated vascular PSMA overexpression has hindered the development and assessment of PSMA-targeting radioligands for imaging and therapy of the nonprostatic cancers.

The Role of the Microbiome in Gastroentero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs).

Gut microbiome balance plays a key role in human health and maintains gut barrier integrity. Dysbiosis, referring to impaired gut microbiome, is linked to a variety of diseases, including cancers, through modulation of the inflammatory process. Most studies concentrated on adenocarcinoma of different sites with very limited information on gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs).

Staphylococcus aureus and Acinetobacter baumannii Inhibit Osseointegration of Orthopedic Implants.

Bacterial infections routinely cause inflammation and thereby impair osseointegration of orthopedic implants. Acinetobacter spp., which cause osteomyelitis following trauma, on or off the battlefield, were, however, reported to cause neither osteomyelitis nor osteolysis in rodents.

Human multipotent adult progenitor cells effectively reduce graft-vs-host disease while preserving graft-vs-leukemia activity.

Graft-vs-host disease (GvHD) limits successful outcomes following allogeneic blood and marrow transplantation (allo-BMT). We examined whether the administration of human, bone marrow-derived, multipotent adult progenitor cells (MAPCs™) could regulate experimental GvHD. The immunoregulatory capacity of MAPC cells was evaluated in vivo using established murine GvHD models.

Small Molecule-Based Prodrug Targeting Prostate Specific Membrane Antigen for the Treatment of Prostate Cancer.

Metastatic castration-resistant prostate cancer poses a serious clinical problem with poor outcomes and remains a deadly disease. New targeted treatment options are urgently needed. PSMA is highly expressed in prostate cancer and has been an attractive biomarker for the treatment of prostate cancer.

Liver background uptake of [F]FLT in PET imaging.

High liver uptake presents a problem for 3'-deoxy-3'-[F]fluorothymidine ([F]FLT) as a radiotracer for imaging cellular proliferation in the liver with positron emission tomography (PET). This investigation re-visited some issues related to the high liver background uptake of [F]FLT with an animal model of woodchucks. Several enzymes involved in the hepatic catabolism of FLT, thymidine phosphorylase (TP, TYMP), uridine 5'-diphospho-glucuronosyl-transferases (UDP-GTs, short for UGTs), and β-glucuronidase (GUSB), their homology as well as hepatic expression between the human and the woodchuck was examined.

A pilot clinical trial of the cytidine deaminase inhibitor tetrahydrouridine combined with decitabine to target DNMT1 in advanced, chemorefractory pancreatic cancer.

DNA methyltransferase 1 (DNMT1) is scientifically validated as a molecular target to treat chemo-resistant pancreatic ductal adenocarcinoma (PDAC). Results of clinical studies of the pyrimidine nucleoside analog decitabine to target DNMT1 in PDAC have, however, disappointed. One reason is high expression in PDAC of the enzyme cytidine deaminase (CDA), which catabolizes decitabine within minutes.

Peritumoral/vascular expression of PSMA as a diagnostic marker in hepatic lesions.

Background: The differential diagnosis between primary cholangiocarcinoma and metastatic pancreatobiliary adenocarcinoma is histologically challenging due to lack of distinct morphological features and reliable molecular markers. Prostate-specific membrane antigen (PSMA) is expressed in prostate epithelium and upregulated on the surface of prostatic adenocarcinoma cells. Studies have shown PSMA enzymatic activity is involved in malignancy-driven neoangiogenesis in the endothelium of tumor-associated neovasculature in breast, lung, thyroid, hepatocellular carcinoma (HCC) and urothelial cancer.

Delayed response to proton beam treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has become one of the leading causes of cancer death worldwide. There has been anecdotal report regarding the effectiveness of proton beam treatment for HCC. In this pre-clinical investigation, the woodchuck model of viral hepatitis infection-induced HCC was used for proton beam treatment experiment.

Synthesis and assessment of ZD2-(Ga-NOTA) specific to extradomain B fibronectin in tumor microenvironment for PET imaging of pancreatic cancer.

Patients diagnosed with pancreatic cancer at a late stage have a dismal survival rate. Accurate early detection of pancreatic cancer with a size of 10 mm or less could dramatically improve patient survival after timely treatments. We have developed a new PET probe ZD2-(Ga-NOTA) specific to extradomain-B fibronectin (EDB-FN), an oncoprotein in tumor microenvironment, for sensitive molecular imaging and early diagnosis of pancreatic cancer.

[F] Clofarabine for PET Imaging of Hepatocellular Carcinoma.

Clinical diagnosis of hepatocellular carcinoma (HCC) relies heavily on radiological imaging. However, information pertaining to liver cancer treatment such as the proliferation status is lacking. Imaging tumor proliferation can be valuable in patient management.

PET imaging of hepatocellular carcinoma with anti-1-amino-3-[F]fluorocyclobutanecarboxylic acid in comparison with L-[S-methyl-C]methionine.

Purpose: [C]methionine ([C]Met) was used for cancer imaging based on upregulated amino acid transport and protein synthesis in different tumor types. However, the short half-life of C decay limited further clinical development of [C]Met. Synthetic amino acid analog anti-1-amino-3-[F]fluoro-cyclobutyl-1-carboxylic acid ([F]FCABC) was developed and FDA-approved for PET imaging of recurrent prostate cancer.

Senescence cell-associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers.

Senescent cells (SnCs) are increasingly recognized as central effector cells in age-related pathologies. Extracellular vesicles (EVs) are potential cellular communication tools through which SnCs exert central effector functions in the local tissue environment. To test this hypothesis in a medical indication that could be validated clinically, we evaluated EV production from SnCs enriched from chondrocytes isolated from human arthritic cartilage.

Preparation and Evaluation of ZD2 Peptide Cu-DOTA Conjugate as a Positron Emission Tomography Probe for Detection and Characterization of Prostate Cancer.

Positron emission tomography (PET) is a sensitive modality for cancer molecular imaging. We aim to develop a PET probe for sensitive detection and risk stratification of prostate cancer by targeting an abundant microenvironment oncoprotein, extradomain-B fibronectin (EDB-FN). The probe consists of a small ZD2 peptide specific to EDB-FN and a Cu-DOTA chelate.

Loss of dihydrotestosterone-inactivation activity promotes prostate cancer castration resistance detectable by functional imaging.

Androgens such as testosterone and dihydrotestosterone are a critical driver of prostate cancer progression. Cancer resistance to androgen deprivation therapies ensues when tumors engage metabolic processes that produce sustained androgen levels in the tissue. However, the molecular mechanisms involved in this resistance process are unclear, and functional imaging modalities that predict impending resistance are lacking.

A novel synthetic route for high-index faceted iron oxide concave nanocubes with high T relaxivity for in vivo MRI applications.

Iron oxide nanoparticles (IONPs) with high-index facets have shown great potential as high performance T contrast agents for MRI. Previous synthetic approaches focused mainly on ion-directed or oxidative etching methods. Herein, we report a new synthetic route for preparing high-index faceted iron oxide concave nanocubes using a bulky coordinating solvent.

Analysis of -5p and -3p Strands of miR-145 and miR-140 During Mesenchymal Stem Cell Chondrogenic Differentiation.

The chondrogenic differentiation of mesenchymal stem cells (MSCs) is mediated by transcription factors and small noncoding RNAs such as microRNAs (miRNAs). Each miRNA is initially transcribed as a long transcript, which matures to produce -5p and -3p strands. It is widely believed that the mature and functional miRNA from any given pre-miRNA, usually the -5p strand, is functional, while the opposing -3p strand is degraded.

Ultrasound-guided Intracardiac Injection of Human Mesenchymal Stem Cells to Increase Homing to the Intestine for Use in Murine Models of Experimental Inflammatory Bowel Diseases.

Crohn's disease (CD) is a common chronic inflammatory disease of the small and large intestines. Murine and human mesenchymal stem cells (MSCs) have immunosuppressive potential and have been shown to suppress inflammation in mouse models of intestinal inflammation, even though the route of administration can limit their homing and effectiveness . Local application of MSCs to colonic injury models has shown greater efficacy at ameliorating inflammation in the colon.

Expression of miR-145-5p During Chondrogenesis of Mesenchymal Stem Cells.

Assessing the quality of tissue engineered (TE) cartilage has historically been performed by endpoint measurements including marker gene expression. Until the adoption of promoter-driven reporter constructs capable of quantitative and real time non-destructive expression analysis, temporal gene expression assessments along a timeline could not be performed on TE constructs. We further exploit this technique to utilize microRNA (miRNA or miR) through the use of firefly luciferase reporter (Luc) containing a 3' UTR perfect complementary target sequence to the mature miR-145-5p.