Search results for "LAB"

A phase I, open-label, dose-escalation trial of BI 764532, a DLL3/CD3 bispecific antibody, in patients (pts) with small cell lung carcinoma (SCLC) or…

2021

TPS8588 Background: First-line standard of care for pts with metastatic SCLC and neuroendocrine carcinoma (NEC) is platinum-based chemotherapy ± immunotherapy. While the addition of anti-PD1 antibodies has improved outcomes, nearly all pts relapse and prognosis is poor. There is a major unmet need for additional treatment (tx) options. BI 764532 is a delta-like ligand 3 (DLL3)/CD3 T cell engaging bispecific antibody. DLL3 is expressed on the cell surface of many SCLC and NEC tumors, but not on normal cells. In preclinical studies, BI 764532 induced cytotoxicity of DLL3-positive cells and showed anti-tumor activity in animal models. Methods: NCT04429087 is a first-in-human, open-label, dose…

Managing Multi-center Flow Cytometry Data for Immune Monitoring.

2014

With the recent results of promising cancer vaccines and immunotherapy 1 – 5 , immune monitoring has become increasingly relevant for measuring treatment-induced effects on T cells, and an essential tool for shedding light on the mechanisms responsible for a successful treatment. Flow cytometry is the canonical multi-parameter assay for the fine characterization of single cells in solution, and is ubiquitously used in pre-clinical tumor immunology and in cancer immunotherapy trials. Current state-of-the-art polychromatic flow cytometry involves multi-step, multi-reagent assays followed by sample acquisition on sophisticated instruments capable of capturing up to 20 parameters per cell at a…

Different patterns of cytokeratin expression in the normal epithelia of the upper respiratory tract

1985

The distribution and type of cytokeratins present in the normal human epithelia of the nasopharynx, oropharynx, tongue, palatine tonsil, epiglottis, vocal cord, and laryngeal ventricle were studied using immunohistochemical techniques and by gel electrophoresis of cytoskeletal proteins microdissected from frozen tissues. Noncornifying stratified epithelia covering the oropharynx, tongue, surface of the palatine tonsil, pharyngeal surface of the epiglottis, and vocal cord were all found to contain cytokeratins nos. 4, 5, 6, 13, 14, and 15, together with minor amounts of cytokeratin no. 19, i.e., a pattern similar to that previously reported for esophageal epithelium. The immunohistochemical …

Site-Specific Dual-Labeling of a VHH with a Chelator and a Photosensitizer for Nuclear Imaging and Targeted Photodynamic Therapy of EGFR-Positive Tum…

2021

Simple Summary Variable domains of heavy chain only antibodies are small proteins that can be used for tumor imaging and therapy upon conjugation of functional groups. As frequently used random conjugation techniques can decrease binding to the target of interest, site-specific conjugation of these functional groups is preferred. Here, we optimized site-specific conjugation of both a chelator for binding of a radiometal and a photosensitizer to epidermal growth factor receptor (EGFR) binding VHH 7D12. We characterized this dual-labeled VHH for nuclear imaging and targeted photodynamic therapy of EGFR-expressing tumors. Abstract Variable domains of heavy chain only antibodies (VHHs) are valu…

Validation of (68)Ge/(68)Ga generator processing by chemical purification for routine clinical application of (68)Ga-DOTATOC.

2008

Abstract Introduction Imaging of somatostatin receptor expressing tumours has been greatly enhanced by the use of 68 Ga-DOTATOC and PET/CT. Methods In this work, a purification method for the 68 Ge/ 68 Ga generator eluate and a method to produce 68 Ga-DOTATOC suitable for clinical use were evaluated. The generator eluate was purified and concentrated on a cation-exchange cartridge in HCl/acetone media. The efficacy of this procedure in eliminating metal impurities from the 68 Ga solution was investigated by ICP-MS. The radiotracer quality was evaluated by radio-TLC, GC and γ-ray spectrometry. Results 68 Ga-DOTATOC preparations ( n =33) were carried out with a mean synthesis yield of 59.3±2.…

Calibration of misonidazole labeling by simultaneous measurement of oxygen tension and labeling density in multicellular spheroids

1995

To correlate misonidazole concentrations and oxygen pressures (Po2) at identical locations within EMT6/Ro multi-cell spheroids (mean diameters +/- SD: 867 +/- 20 microns), Po2 measurements were performed with oxygen-sensitive microelectrodes during incubation of these spheroids with tritiated misonidazole (10 mg/I; 445 microCi/mg). In each individual spheroid, Po2 profiles were correlated with the corresponding spatial distribution of misonidazole as quantified by conventional autoradiography and grain counting. To compare the oxygenation status of spheroids in the measuring chamber with that of spheroids in spinner culture, misonidazole labeling was performed in both environments following…

Labeling and preliminary in vivo assessment of niobium-labeled radioactive species: A proof-of-concept study.

2016

Abstract The application of radionuclide-labeled biomolecules such as monoclonal antibodies or antibody fragments for imaging purposes is called immunoscintigraphy . More specifically, when the nuclides used are positron emitters, such as zirconium-89, the technique is referred to as immuno-PET . Currently, there is an urgent need for radionuclides with a half-life which correlates well with the biological kinetics of the biomolecules under question and which can be attached to the proteins by robust labeling chemistry. 90 Nb is a promising candidate for in vivo immuno-PET , due its half-life of 14.6h and low β + energy of E mean =0.35MeV per decay. 95 Nb on the other hand, is a convenient …

P105. New findings on vasodilator potency, tachyphylaxis, and bioavailability of organic nitrates reveal: The tolerance-devoid clinical action of pen…

2006

In BCR-ABL-positive cells, STAT-5 tyrosine-phosphorylation integrates signals induced by imatinib mesylate and Ara-C.

2003

In BCR-ABL-positive cells, the transcription factor STAT-5 is constitutively activated by tyrosine phosphorylation. STAT-5 activation results in upregulation of bcl-X(L) and increased resistance to induction of apoptosis. Here, we investigated the effects of imatinib mesylate and cytosine arabinoside (Ara-C) on STAT-5 tyrosine-phosphorylation, cellular proliferation and induction of apoptosis in cell lines and primary hematopoietic cells. Imatinib mesylate treatment strongly suppressed STAT-5 tyrosine-phosphorylation in K562 and primary CML blasts. In contrast to JAK-2 and PI-3-kinase inhibition, exposure of K562 cells to imatinib mesylate resulted in obvious suppression of proliferation. R…

Cell Harvesting Methods Affect Cellular Integrity of Adherent Cells During Apoptosis Detection.

2018

Background/aim Annexin V and propidium iodide (PI) dual staining is commonly applied in bioscience as a method to detect apoptosis. However, excessive handling of adherent cells may interfere with the integrity of plasma membrane and hence impede the accuracy of this method. Here, we exploited PI uptake as an indicator of cell integrity and investigated how cell harvesting methods and solutions involved in common apoptosis detection techniques affected measurement results. Materials and methods Different cell harvesting techniques, staining with PI and flow cytometry were performed. Results Non-fixed scrapped cells revealed significantly higher fractions of PI-positive staining compared to …