Chemical modulation of chemotherapy resistance in cultured oesophageael carcinoma cells

Abstract

Age related deterioration in immune function has been recognised in many species. In humans the clinical manifestations of such immune dysfunction is an age-related increase in the susceptibility to certain infections, the incidence of some autoimmune diseases and certain cancers. Laboratory investigations reveal age-related changes in the peripheral T cell pool, in the predominant phenotype, cytokine production profiles, signaling function, and in replicative ability following stimulus with antigen, mitogens or anti CD3 antibody. These changes in the properties of peripheral T cells are thought to be causally linked to an age-associated involution in the thymus. Our analysis reveals that thymic involution is due to a change in the thymic microenvironment linked to a reduction in the levels of available IL-7. Treatment with IL-7 leads to a reversal of thymic atrophy with increased thymopoiesis. This provides the potential to reverse the immune dysfunction seen in the peripheral T cell pool by replacing old T cells with new output generated by the thymus. Problems to overcome for such an experimental therapy to be successful require careful analysis in order to provide an optimal strategy to ensure that new T cell emigrants from the thymus have a broad range of specificities and are able to enter the peripheral T cell pool.

A Pilot Trial of Combination Cisplatin, 5-Fluorouracil and Interferon-α in the Treatment of Advanced Esophageal Carcinoma

“…Findings were suggestive of a possible role for glutathione S-transferase and/or glutathione [25]. This pattern of resistance seemed to exclude the multidrug resistance phenotype.…”

“…This pattern of resistance seemed to exclude the multidrug resistance phenotype. Recent efforts to deplete glutathione S-transferase have failed to overcome drug resistance [25].…”