Aphton Corp.

The immunoglobulin molecule contains structural features that make it a powerful tool for cancer therapy (eg, an extremely high specificity and binding affinity for the target molecule that results in low toxicity). Several approaches have been used: monoclonal antibodies targeting a ligand (eg, bevacizumab, anti-vascular endothelial growth factor), monoclonal antibodies targeting a receptor (eg, cetuximab, anti-epidermal growth factor receptor), vaccines targeting a ligand (eg, G17DT, anti-gastrin), or a cell surface antigen (eg, carcinoembryonic antigen-TRIad of COstimulatory Molecules, anti-CEA). Another approach attempts to harness the cellular arm of the immune response (ie, cytotoxic T cells, natural killer cells) for specific killing of tumor cells. The putative underlying mechanism of antibody strategy is the inhibition of intracellular signaling pathways and induction of apoptosis. Clinical evidence suggests that while most of these antibodies achieve limited antitumor activity as monotherapy, they are significantly more efficacious than single agents when combined with chemotherapy. Future use of these agents will include optimized combination chemotherapy/immunotherapy regimens as well as monoclonal antibodies conjugated to cytotoxic molecules and radionuclides.

Abstract Historically, the interplay between basic research and clinical observation has been essential in the development of new therapies for peptic ulcer disease. That histamine is an important regulator of acid secretion emerged from basic research, followed by the clinical development and use of the H2‐receptor antagonists. Basic research contributed again by defining the importance of H+/K+‐ATPase in acid secretion, resulting in a new class of useful antisecretory agents. Basic studies also gave us prostaglandins (PG) as mucosal protective agents. As ‘replacement’ therapy, clinicians have found that PG are protective against non‐steroidal anti‐inflammatory drug (NSAID)‐induced gastric ulcer (GU). Physiologic studies established that somatostatin is a potent inhibitor of acid secretion, providing the stimulus for clinical studies in Zollinger‐Ellison (ZE) Syndrome with a synthetic analog (octreotide). Work on isoforms of the parietal cell gastrin receptor has shown differences in the cytoplasmic domain for G protein coupling. This will aid in understanding how receptor changes and coupling to second messengers relate to the aetiopathogenesis of abnormal gastric secretion. Immune cells express mRNA for histamine, muscarinic and gastrin receptors, supporting the relevance of mucosal immunology in gastroenterology, especially in light of Helicobacter pylori‐associated gastritis and ulcers. Lab research has revealed a potential role for basic fibroblast growth factor (bFGF), and another endogenous peptide BPC‐15, in ulcer healing. The former substance may be responsible for the antiulcer efficacy of sucralfate. Intensive basic work on how H. pylori organisms attach to gastric cells and initiate inflammatory reactions in the mucosa will have unquestionable impact on improved therapy for peptic ulcer disease.