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Biomedical subjects

D Kessel

Publications and source records attributed to D Kessel.

At least 163 records · Page 9Linked to original sources
PubMed1987

Probing the structure and stability of the tumor-localizing derivative of hematoporphyrin by reductive cleavage with LiAlH4.

A procedure involving the use of the reducing agent lithium aluminum hydride (LiAlH4) has been designed to explore the nature of the oligomer linkages in the tumor-localizing component of hematoporphyrin derivative (HPD). High-performance liquid chromatography and fast-atom bombardment mass spectrometry were used to determine the reduction products. The results are consistent with a structure wherein ester linkages join hematoporphyrin molecules. The presence of minor amounts of ether-linked porphyrins was confirmed, and their origin was determined through the application of the chemical reduction process to HPD. An increased proportion of ether-linked porphyrins was detected during storage of HPD at room temperature or above. The commercial product Photofrin II, presumably an HPD preparation enriched in the dimer/oligomer fraction, was found to contain approximately 50% ether linkages. This product therefore differs from the corresponding fraction of freshly prepared HPD.

Aluminum↗
PubMed1986

Intracellular glutathione as a determinant of responsiveness to antitumor drugs.

The effect of glutathione depletion on cytotoxicity of the anthracycline daunorubicin, and of a copper:bis-thiosemicarbazone chelate, was examined in the P388 murine leukemia and its anthracycline-resistant subline, P388/ADR. Depletion of intracellular glutathione was accomplished through exposure to buthionine sulfoximine, a specific inhibitor of glutathione synthesis. Cytotoxicity of daunorubicin was not altered by glutathione depletion, while responsiveness to the bis-thiosemicarbazone chelate was thereby enhanced.

Antibiotics, Antineoplastic↗
PubMed1986

Porphyrin-lipoprotein association as a factor in porphyrin localization.

Systemic administration of the tumor-localizing product hematoporphyrin derivative (HPD) to mice bearing the Lewis-Lung tumor leads to an initial distribution of porphyrins among plasma lipoproteins and albumin. The more hydrophobic components of HPD (including the tumor-localizing fraction) preferentially bind to plasma low density lipoprotein (LDL) and high density lipoprotein (HDL). After 48 h, the remaining plasma porphyrins are mainly bound to HDL. The distribution pattern of HPD is correlated with the relative numbers of LDL receptors in different tissues.

Animals↗
PubMed1986

Photosensitization with derivatives of haematoporphyrin.

This review describes recent progress in delineation of the structure of the active component(s) in the tumour-localizing photosensitizer HPD (haematoporphyrin derivative), along with suggestions concerning the likely determinants of accumulation of this product by different tissues.

Hematoporphyrin Derivative↗
PubMed1986

Circumvention of resistance to anthracyclines by calcium antagonists and other membrane-perturbing agents.

Resistance to a variety of naturally occurring antitumour agents, including the anthracyclines, vinca alkaloids and actinomycin D, is associated with an outward transport system which limits intracellular drug accumulation to sublethal levels. A series of agents of unrelated structure, including calcium and calmodulin antagonists, local anaesthetics and detergents, can impair this outward transport system, and thereby promote cytotoxicity of these antitumour agents. These effects are not related to alterations in calcium fluxes, but appear to derive from membrane perturbations which also affect other transport systems. There are additional modes of drug resistance not based on transport alterations which are apparently unaffected by these second agents.

Anesthetics, Local↗
PubMed1986

Localization and photosensitization of murine tumors in vivo and in vitro by a chlorin-porphyrin ester.

Preparation of the tumor-localizing preparation called hematoporphyrin derivative involves a two-step reaction wherein hematoporphyrin is acetylated and the reaction product subjected to alkaline hydrolysis. We have proposed that the tumor-localizing fraction of this product is composed of hematoporphyrin units joined by ester linkages. Using an analogous synthetic procedure, we prepared some new sensitizers in which hematoporphyrin is esterified to chlorins (reduced porphyrins). Because of the differences in absorption spectra, the porphyrin-chlorin esters are 5-fold more potent photosensitizers than are the porphyrin-porphyrin esters, with light of wavelength greater than 600 nm.

Animals↗
PubMed1986

Photosensitization of leukemia L1210 cells with diaziquone.

Exposure of leukemia L1210 cells in culture to the drug diaziquone resulted in inhibition of incorporation of labeled thymidine into nucleic acid and loss of cell viability. These effects were markedly potentiated by irradiation of cells previously exposed to diaziquone in culture. This result shows that diaziquone can catalyze phototoxicity; the action spectrum of the drug may limit clinical applications of this phenomenon.

Animals↗