Potentiation of the antitumor effect of Merocyanine 540-mediated photodynamic therapy by amifostine and amphotericin B

Leukemia and lymphoma cells are much more sensitive to Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) than normal pluripotent hematopoietic stem cells and normal colony forming unit-granulocyte/macrophage progenitors (CFU-GM). By contrast, most solid tumor cells are only moderately sensitive to MC540-PDT. The limited activity against solid tumor cells has detracted from MC540's appeal as a broad-spectrum purging agent. We report here that noncytotoxic concentrations of amifostine (Ethyol, Ethiofos, WR-2721) and amphotericin B used either alone or in combination potentiate the MC540-sensitized photoinactivation of leukemia cells, wild-type small cell lung cancer cells and cisplatin-resistant small cell lung cancer cells. Amphotericin B also enhances the MC540-sensitized photoinactivation of normal CFU-GM, whereas amifostine protects CFU-GM against the cytotoxic action of MC540-PDT. The yield of CD34-positive normal hematopoietic stem and progenitor cells is only minimally diminished by pretreatment with amifostine, amphotericin B or combinations of amifostine plus amphotericin B. Purging protocols that combine MC540-PDT with amifostine or with amifostine plus amphotericin B could offer a simple and effective approach to the purging of autologous stem cell grafts that are contaminated with solid tumor cells or the purging of stem cell grafts from heavily pretreated leukemia patients that contain reduced numbers of normal stem and progenitor cells and, therefore, can ill afford additional losses caused by purging.     

Amino acid-bearing ROMP polymers with a stereoregular backbone

The ruthenium-catalyzed ring-opening polymerization (ROMP) of 1-cyclobutenecarbonyl glycine methyl ester provides translationally invariant, head-to-tail ordered polymers. This polybutadiene backbone contains (within the limits of detection) only E-trisubstituted olefins, and it has no stereocenters that would serve as a source of structural ambiguities. Characterization of the polymer products indicates that they have polydispersities ranging from 1.2 to 1.6 and suggests that they are the products of a "living" polymerization. 1-Cyclobutenecarboxamide-derived ROMP polymers are excellent prospects for applications that require stereoregular chains functionalized with polar ligands.     

Generation of multiply charged peptides and proteins by radio frequency acoustic desorption and ionization for mass spectrometric detection

The design and implementation of a radio frequency acoustic desorption ionization (RADIO) source has been demonstrated for the analysis of multiply charged peptides and proteins. One μL aliquots of melittin, BNP-32, and ubiquitin (∼1 μg of analyte) were deposited onto a quartz crystal microbalance (QCM) electrode before radio frequency actuation for desorption. Continuous electrospray parallel to/above the sampling surface enabled the ionization of desorbed species. Detection by a hybrid linear ion trap Fourier transform ion cyclotron resonance mass spectrometer confirmed the intact and dissociated species observed during MS and MS/MS experiments, respectively.