ABSTRACT
To evaluate the accuracy of a new fluorine-18-2-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) method when applying an increased upper limit of the image threshold (IULIT) to detect bladder cancer. All patients with an unknown history of bladder tumors were retrospectively included for analysis. Applying an IULIT in PET showed a hypermetabolic focus. (18)F-FDG accumulation in the bladder that was higher or lower than the urinary level of (18)F-FDG was considered an abnormal focus. In 12 of the 28,767 patients with bladder cancer, applying an IULIT in PET allowed the visualization of the contrast between lesion and urinary activity. The proposed method could increase the accuracy of detection of bladder cancer.
Subject(s)
Fluorodeoxyglucose F18 , Positron-Emission Tomography/methods , Tomography, X-Ray Computed/methods , Urinary Bladder Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Female , Humans , Image Interpretation, Computer-Assisted , Image Processing, Computer-Assisted , Male , Middle Aged , Reproducibility of Results , Sensitivity and Specificity , Tumor Burden , Urinary Bladder Neoplasms/pathologyABSTRACT
PURPOSE: To evaluate the toxicity, immunogenicity, and pharmacokinetics of a human-mouse chimeric monoclonal antibody (mAb) ch 14.18 directed against disialoganglioside (GD2) and to obtain preliminary information on its clinical efficacy, we conducted a phase I trial in 10 patients with refractory neuroblastoma and one patient with osteosarcoma. PATIENTS AND METHODS: Eleven patients were entered onto this phase I trial. They received 20 courses of mAb ch 14.18 at dose levels of 10, 20, 50, 100, and 200 mg/m2. Dose escalation was performed in cohorts of three patients; intrapatient dose escalation was also permitted. RESULTS: The most prevalent toxicities were pain, tachycardia, hypertension, fever, and urticaria. Most of these toxicities were dose-dependent and rarely noted at dosages of 20 mg/m2 and less. Although the maximum-tolerated dose was not reached in this study, clinical responses were observed. These included one partial (PR) and four mixed responses (MRs) and one stable disease (SD) among 10 assessable patients. Biologic activity of ch 14.18 in vivo was shown by binding of ch 14.18 to tumor cells and complement-dependent cytotoxicity of posttreatment sera against tumor target cells. An anti-ch 14.18 immune response was detectable in seven of 10 patients studied. CONCLUSION: In summary, with the dose schedule used, ch 14.18 appears to be clinically safe and effective, and repeated mAb administration was not associated with increased toxicities. Further clinical trials of mAb ch 14.18 in patients with neuroblastoma are warranted.
Subject(s)
Antibodies, Monoclonal/metabolism , Antibodies, Monoclonal/therapeutic use , Gangliosides/immunology , Neuroblastoma/therapy , Osteosarcoma/therapy , Adult , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Child , Child, Preschool , Complement C3/analysis , Complement C4/analysis , Complement Hemolytic Activity Assay , Female , Fluorescent Antibody Technique, Indirect , Humans , Infusions, Intravenous , Male , Mice , Neuroblastoma/metabolism , Pain/chemically induced , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/metabolism , Recombinant Fusion Proteins/therapeutic use , Treatment OutcomeABSTRACT
Stimulus-linked RNA and protein synthesis is required for establishment of long-term neuroplasticity. To identify molecular mechanisms underlying long-term neuroplasticity, we have used differential cDNA techniques to clone a novel immediate-early gene (IEG) that is rapidly induced in neurons of the hippocampus and cortex by physiological synaptic activity. Analysis of the deduced amino acid sequence indicates homology to members of the pentraxin family of secreted lectins that include C-reactive protein and serum amyloid P component. Regions of homology include an 8 amino acid "pentraxin signature" sequence and a characteristic pentraxin calcium-binding domain. We have termed this gene and the encoded protein Narp (from neuronal activity-regulated pentraxin). Biochemical analyses confirm the presence of a functional signal sequence, and Narp is secreted by transfected COS-1 cells in culture. Additionally, Narp binds to agar matrix in a calcium-dependent manner consistent with the lectin properties of the pentraxin family. When cocultured with Narp-secreting COS-1 cells, neurons of cortical explants exhibit enhanced growth of neuronal dendritic processes. Neurite outgrowth-promoting activity is also observed using partially purified Narp and can be specifically immunodepleted, demonstrating that Narp is the active principle. Narp is fully active at a concentration of approximately 40 ng/ml, indicating a potency similar to known peptide growth factors. Because Narp is rapidly regulated by neuronal activity, its lectin and growth-promoting activities are likely to play role in the modification of cellular properties that underlie long-term plasticity.
