metrizamide and Neoplasms

Glucose, the primary substrate for ATP synthesis, is catabolized during glycolysis to generate ATP and precursors for the synthesis of other vital biomolecules. Opportunistic viruses and cancer cells often hijack this metabolic machinery to obtain energy and components needed for their replication and proliferation. One way to halt such energy-dependent processes is by interfering with the glycolytic pathway. 2-Deoxy-d-glucose (2-DG) is a synthetic glucose analogue that can inhibit key enzymes in the glycolytic pathway. The efficacy of 2-DG has been reported across an array of diseases and disorders, thereby demonstrating its broad therapeutic potential. Recent approval of 2-DG in India as a therapeutic approach for the management of the COVID-19 pandemic has brought renewed attention to this molecule. The purpose of this perspective is to present updated therapeutic avenues as well as a variety of chemical synthetic strategies for this medically useful sugar derivative, 2-DG.

Topics: Adenosine Triphosphate; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Deoxyglucose; Epilepsy; Glycolysis; Humans; Isotope Labeling; Mitochondria; Neoplasms; Positron-Emission Tomography; SARS-CoV-2; Structure-Activity Relationship; Virus Replication

Eosinophils are multifunctional leukocytes classically described as being involved in helminth parasitic infections and allergic diseases. Previously restricted to an exclusive role in the release of cytotoxic mediators, they are now also considered to be immunoregulatory cells and potential effectors in innate immune responses. Eosinophils are mainly found in tissues, so specific procedures are needed for their isolation from venous blood and for functional assays. Murine models are very useful for the dissection of eosinophil physiology in vivo. But murine eosinophils significantly differ from human ones. A complete understanding of eosinophil biology therefore requires comparative study of eosinophils from different mammalian species. We summarize here the main experimental protocols used to study human, mouse, and rat eosinophil biology. We focus on technical improvements of existing methods that optimize purification and in vitro functional studies of eosinophils.

Topics: Animals; Biomarkers; Cell Culture Techniques; Cell Separation; Cells, Cultured; Cytotoxicity, Immunologic; Eosinophils; Flow Cytometry; Humans; Immunity, Innate; Metrizamide; Mice; Neoplasms; Rats; Receptors, Immunologic; Solutions

Specific targeting of liposome-formulated cytotoxic drugs or antigens to receptors expressed selectively on target cells represents an effective strategy for increasing the pharmacological efficacy of the delivered molecules. We have developed a feasible technique to selectively attach antibodies and fragments thereof, but also small-mol-wt ligands such as peptides, carbohydrates, or any molecules that recognize and bind target antigens or receptors to the surface of small unilamellar liposomes. Our concept is based on the site-specific functionalization of the ligands to be attached to the liposomes by thiol groups. These thiol groups can easily be introduced to antibodies or peptides by addition of cysteines, preferably at sites that do not interfere with the receptor binding domains. Optimally, the site-specific modification is introduced at the C-terminal end of the ligand, separated by an inert spacer sequence located between the thiols and the specific part of the ligand. The thiol-reactive molecules on the liposome surface are maleimides that are linked to phospholipids composing the liposome bilayer membrane. We illustrate the coupling method of a functionalized single-chain antibody fragment with binding specificity to ED-B fibronectin, an isoform of fibronectin exclusively expressed in tumor tissues, to long circulating small unilamellar poly(ethylene glycol) liposomes.

Topics: Cell Line, Tumor; Drug Delivery Systems; Humans; Immunoglobulin Fragments; Lipids; Liposomes; Metrizamide; Molecular Structure; Neoplasms

New lesions were shown by Tc99m bone scans to have developed in sixty patients with known metastatic cancer or high-risk primary cancer and normal neurologic examinations; they were further evaluated with plain radiographs, spinal computed tomography (CT), and CT myelography (CT-M) according to an algorithm. Three groups were identified based on plain radiographs: group 1 (normal radiograph), group 2 (compression fracture as indicated by radiograph), group 3 (evidence of metastasis as indicated by radiograph). In group 1 (n = 18), spinal CT revealed that 33% of the patients had benign disease and 67%, metastases; epidural compression was seen in 25% of the patients with metastasis as indicated by CT-M. In group 2 (n = 26), CT-M disclosed that 38% had a benign compression fracture and 62% had metastases and that 63% of the patients with metastases had an epidural compression. In group 3 (n = 16), spinal CT revealed that 15 patients had metastases (one patient had benign disease). Epidural cord compression was seen in 47% of the patients with metastatic disease. In all groups, the presence of cortical bone discontinuity around the neural canal (seen in 31 patients) was highly associated with epidural compression (seen in 20 patients). Our approach allowed the early and accurate diagnosis of spinal metastasis and epidural tumor as well as the diagnosis of benign disease and was useful in planning optimal local therapy.

Topics: Bone and Bones; Female; Humans; Male; Metrizamide; Myelography; Neoplasm Metastasis; Neoplasms; Spinal Neoplasms; Spine; Technetium; Tomography, X-Ray Computed