ABSTRACT
Bryostatin 1, isolated from a marine bryozoan, enhances the efficacy of cytotoxic agents through modulation of the protein kinase C pathway and is active in combination with vincristine for diffuse large B-cell lymphoma. Further, the apoptotic frequency of peripheral blood T lymphocytes as determined by flow cytometry may predict which patients will respond to this combination. We tested the efficacy and safety of bryostatin 1 50 microg/m(2) given over 24 hr and vincristine 1.4 mg/m(2) on days 1 and 15 every 28 days in aggressive B-cell non-Hodgkin lymphoma (NHL) relapsing after autologous stem cell transplantation. End points included tumor response, toxicity, and survival. Responses were correlated with an increase in apoptotic frequency of CD5+ cells by flow cytometry using annexin V staining. Fourteen patients were enrolled with 13 being evaluable for a response. The overall response rate was 31% with two patients achieving a complete response. The most common toxicities were Grade 3 lymphopenia (seven patients), Grade 3 to 4 neutropenia (two patients), and Grade 3 hypophosphatemia (two patients). Median progression-free and overall survivals for all patients were 5.7 and 21.4 months, respectively. One patient demonstrated an increase in T-cell apoptotic frequency, also achieving a complete response. Bryostatin 1 and vincristine have efficacy in select patients with aggressive NHL. Future investigations of agents targeting the protein kinase C pathway may benefit from early response assessment using flow cytometry to evaluate T-cell apoptosis.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Lymphoma, B-Cell/prevention & control , Stem Cell Transplantation , Aged , Annexin A5/metabolism , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Apoptosis/drug effects , Bryostatins/administration & dosage , Bryostatins/adverse effects , CD5 Antigens/blood , Disease-Free Survival , Female , Humans , Lymphoma, B-Cell/blood , Lymphopenia/blood , Lymphopenia/chemically induced , Male , Middle Aged , Protein Kinase C/metabolism , Recurrence , Survival Rate , T-Lymphocytes/metabolism , Transplantation, Autologous , Vincristine/administration & dosage , Vincristine/adverse effectsABSTRACT
We have investigated the electrochemical oxidation of a number natural phenolics (salicylic acid, m-hydroxybenzoic acid, p-hydroxybenzoic acid, protocatechuic acid, o-coumaric acid, m-coumaric acid, p-coumaric acid, caffeic acid, quercetin and rutin) using cyclic voltammetry. The antioxidant properties of these compounds were also studied. A structural analysis of the tested phenolics suggests that multiple OH substitution and conjugation are important determinants of the free radical scavenging activity and electrochemical behavior. Compounds with low oxidation potentials (Epa lower than 0.45) showed antioxidant activity, whereas compounds with high Epa values (>0.45) act as prooxidants.
