PSMA as a Theranostic Target in Hepatocellular Carcinoma: Immunohistochemistry and Ga-PSMA-11 PET Using Cyclotron-Produced Ga.

Prostate-specific membrane antigen (PSMA) is a validated target for molecular diagnostics and targeted radionuclide therapy. Our purpose was to evaluate PSMA expression in hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and hepatic adenoma (HCA); investigate the genetic pathways in HCC associated with PSMA expression; and evaluate HCC detection rate with Ga-PSMA-11 positron emission tomography (PET). In phase 1, PSMA immunohistochemistry (IHC) on HCC (n = 148), CCA (n = 111), and HCA (n = 78) was scored.

Automatic and Reliable Quantification of Tonic Dopamine Concentrations Using a Novel Probabilistic Inference Method.

Dysregulation of the neurotransmitter dopamine (DA) is implicated in several neuropsychiatric conditions. Multiple-cyclic square-wave voltammetry (MCSWV) is a state-of-the-art technique for measuring tonic DA levels with high sensitivity (<5 nM), selectivity, and spatiotemporal resolution. Currently, however, analysis of MCSWV data requires manual, qualitative adjustments of analysis parameters, which can inadvertently introduce bias.

Advances in neurochemical measurements: A review of biomarkers and devices for the development of closed-loop deep brain stimulation systems.

Neurochemical recording techniques have expanded our understanding of the pathophysiology of neurological disorders, as well as the mechanisms of action of treatment modalities like deep brain stimulation (DBS). DBS is used to treat diseases such as Parkinson's disease, Tourette syndrome, and obsessive-compulsive disorder, among others. Although DBS is effective at alleviating symptoms related to these diseases and improving the quality of life of these patients, the mechanism of action of DBS is currently not fully understood.

Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model.

BackgroundLocal recurrence following thermal ablation of hepatocellular carcinoma (HCC) larger than 2-3 cm remains a challenging clinical problem. Prior studies suggest that phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)-dependent protein kinase B (AKT) signaling mediates HCC cell survival caused by moderate heat stress in vitro but these findings need in vivo validation.PurposeTo test the hypothesis that neoadjuvant inhibition of PI3K/mTOR/AKT signaling reduces HCC tumor growth in vivo after laser ablation and to evaluate the effects of moderate heat stress on molecular signaling and cellular function in HCC cells in vitroMaterials and MethodsHCC tumor-bearing mice were randomized to neoadjuvant PI3K/mTOR inhibitor (BEZ235) or control groups followed by an intentional partial laser ablation or sham ablation; there were at least nine mice per group.

New and Emerging Applications of Magnetic Resonance Elastography of Other Abdominal Organs.

Increasing clinical experience and ongoing research in the field of magnetic resonance elastography (MRE) is leading to exploration of its applications in other abdominal organs. In this review, the current research progress of MRE in prostate, uterus, pancreas, spleen, and kidney will be discussed. The article will describe patient preparation, modified technical approach including development of passive drivers, modification of sequences, and inversion.

Heat Stress and Thermal Ablation Induce Local Expression of Nerve Growth Factor Inducible (VGF) in Hepatocytes and Hepatocellular Carcinoma: Preclinical and Clinical Studies.

The purposes of this study were to test the hypothesis that heat stress and hepatic thermal ablation induce nerve growth factor inducible (VGF) and to determine intrahepatic versus systemic VGF expression induced by thermal ablation in vivo and in patients. Hepatocytes and HCC cells were subjected to moderate (45°C) or physiologic (37°C) heat stress for 10 min and assessed for VGF expression at 0-72 h post-heat stress ( ≥ 3 experiments). Orthotopic N1S1 HCC-bearing rats were randomized to sham or laser thermal ablation (3 W × 90 s), and liver/serum was harvested at 0-7 days postablation for analysis of VGF expression ( ≥ 6 per group).

Heat Stress and Hepatic Laser Thermal Ablation Induce Hepatocellular Carcinoma Growth: Role of PI3K/mTOR/AKT Signaling.

Purpose To determine if heat stress and hepatic laser thermal ablation induce hepatocellular carcinoma (HCC) growth and to identify growth factors induced by heat stress. Materials and Methods Non-heat-stressed HCC cells were cocultured with HCC cells or hepatocytes that were heat stressed at 37°C (physiologic), 45°C (moderate), or 50°C (severe) for 10 minutes and proliferation monitored with bioluminescence imaging for up to 6 days after heat stress (three experiments). Rats bearing orthotopic N1S1 HCC were randomly assigned to undergo immediate sham or laser thermal (3 W for 60 or 90 seconds; hereafter, 3W×60s and 3W×90s, respectively) ablation of the median (local) or left (distant) hepatic lobe, and tumor growth was monitored with magnetic resonance imaging for up to 18 days after ablation (six or more rats per group).

Heat stress induced, ligand-independent MET and EGFR signalling in hepatocellular carcinoma.

Purpose: The aims of the present study were 2-fold: first, to test the hypothesis that heat stress induces MET and EGFR signalling in hepatocellular carcinoma (HCC) cells and inhibition of this signalling decreases HCC clonogenic survival; and second, to identify signalling pathways associated with heat stress induced MET signalling.

Materials And Methods: MET and EGFR HCC cells were pre-treated with inhibitors to MET, EGFR, PI3K/mTOR or vehicle and subjected to heat stress or control ± HGF or EGF growth factors and assessed by colony formation assay, Western blotting and/or quantitative mass spectrometry. IACUC approved partial laser thermal or sham ablation was performed on orthotopic N1S1 and AS30D HCC tumours and liver/tumour assessed for phospho-MET and phospho-EGFR immunostaining.

Uterine fibroids: correlations between MRI appearance and stiffness via magnetic resonance elastography.

Rationale And Objectives: Magnetic resonance elastography has proven to be a valuable tool in the diagnosis of liver fibrosis, breast and cervical cancer, but its application in uterine fibroids requires further characterization. The aim of the present study was to examine the relationship between uterine fibroid stiffness by MRE and MR imaging characteristics.

Materials And Methods: An IRB-approved, HIPAA compliant review was performed of prospectively collected pelvic MRI and 2D-MRE data in patients with symptomatic uterine fibroids (N = 102).

MRI-guided Wire Localization Surgical Biopsy in an Adolescent Patient with a Difficult to Diagnose Case of Lymphoma.

A 17-year-old previously healthy female presented with a progressive soft tissue infiltrative process involving the neck and thorax. Extensive diagnostic evaluation including multiple imaging, laboratory, and biopsy studies was nondiagnostic. Due to an urgent need to establish a diagnosis and several previous nondiagnostic biopsies, she was referred to interventional radiology for MRI-guided wire localization immediately prior to open surgical biopsy.

Heat Stress-Induced PI3K/mTORC2-Dependent AKT Signaling Is a Central Mediator of Hepatocellular Carcinoma Survival to Thermal Ablation Induced Heat Stress.

Thermal ablative therapies are important treatment options in the multidisciplinary care of patients with hepatocellular carcinoma (HCC), but lesions larger than 2-3 cm are plagued with high local recurrence rates and overall survival of these patients remains poor. Currently no adjuvant therapies exist to prevent local HCC recurrence in patients undergoing thermal ablation. The molecular mechanisms mediating HCC resistance to thermal ablation induced heat stress and local recurrence remain unclear.