Chemical and biochemical determinants of porphyrin localization.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to D Kessel.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Serum sialyltransferase (SST) activity was measured 10 days after mastectomy in 153 patients with operable breast cancer. Enzyme activity declined with time in storage (1-42 months). After correction for loss of activity in storage, patients with SST activity below the median value had a longer disease-free interval (DFI) than those with SST activity above the median, and this difference remained when patients were stratified by axillary nodal status, tumor size, and tumor grade. Survival was longer in patients with low SST activity. Post-operative elevation of SST indicates a poor prognosis in patients with operable breast cancer.
Explore the source record for details and available documents.
Synthetic and analytical approaches were used to characterize the tumor-localizing components of the porphyrin preparation, hematoporphyrin derivative. From studies involving aqueous and nonaqueous gel exclusion and reverse-phase chromatography, we conclude that localization is mediated by hematoporphyrin derivative components which are among the most hydrophobic in the preparation. This apparent hydrophobicity may derive from hydrogen-bonding phenomena, rather than from absence of hydrophilic functional groups.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Serum sialyl transferase (SST) was measured in 49 female patients with advanced breast cancer and 60 female controls. The mean SST level was significantly raised in patients with advanced breast cancer. There was no correlation between specific sites, or numbers of sites of metastatic disease and SST levels. The patients with advanced breast cancer were all treated with chemotherapy; in 13/21 responders there was a significant fall in SST and in 2 responders a significant rise in SST. The 6 patients who died after one course of chemotherapy had a significantly higher mean SST than those surviving longer. SST appears to lack sufficient specificity to be of practical value as a marker of response in patients with breast cancer treated by chemotherapy, though constant measurement of changes in SST may be of use in monitoring drug response. Raised SST at the commencement of chemotherapy may signify poor prognosis.
Explore the source record for details and available documents.
Hematoporphyrin derivative (HPD), a complex mixture of porphyrins derived from hematoporphyrin, has been used for localization and photoradiation therapy of tumors. In this report, we describe characterization of HPD and of its component porphyrins by reverse-phase thin-layer chromatography. Uptake of major HPD components by leukemia L1210 cells in vitro and by the Sarcoma 180 tumor in vivo were also examined. These data suggest that the apparent photosensitization of intact cells mediated by hematoporphyrin was associated with the uptake of more hydrophobic porphyrins present as impurities. In the Sarcoma 180 tumor, the fluorescent porphyrin persisting for two days in vivo after HPD administration was found to migrate with hematoporphyrin in a reverse-phase thin-layer chromatography system. Our results suggest that hematoporphyrin may be unable to cross the cell membrane readily in either direction and that long-persisting fluorescence resulting from exposure of tumor tissues to HPD results from transformation of a membrane-permeable HPD component to hematoporphyrin.
Partitioning behavior of murine lymphoblasts was examined in biphasic aqueous systems containing dextran and poly(ethylene glycol) with no potential difference across the interface. Persistence of cells in the upper phase of the system could be promoted by addition of the palmitate ester of poly(ethylene glycol). Partitioning effects seen here may derive from affinity of membrane sialic acid residues for dextran-rich lower-phase droplets, and antagonism of these interactions by poly(ethylene glycol) palmitate. Several determinants of partitioning behavior were examined: 1. Membrane glycosylation. Partitioning behavior of P388 and P388/ADR lymphoblasts were compared. The latter has an inherently higher degree of membrane glycosylation, resulting in a lower partition coefficient in poly(ethylene glycol) palmitate-supplemented systems. 2. Degree of esterification. Singly-esterified poly(ethylene glycol) was substantially more effective at promoting cell partition into the upper phase than was doubly-esterified glycol. Use of the latter was associated with cell-cell aggregation. 3. Relative numbers of lower-phase droplets present. Decreasing the numbers of such droplets initially present markedly increased the partition coefficient. 4. Time-dependence. Even in the presence of poly(ethylene glycol) palmitate, the partition coefficient fell with time, indicating an interaction between cells and lower-phase droplets not antagonized by the ester.
Explore the source record for details and available documents.
L-Fucose and D-galactose in low concentrations (0.27 or 2.7 mM) inhibited the induction of active Na+ channels in mouse and human neuroblastoma cells when the monosaccharides were added to the culture medium for 4 days with the inducing agent dimethyl sulfoxide. Active Na+ ionophores were determined by measurement of the toxin-stimulated efflux of 86Rb from the cells. At the same time, the amount of a radioactive glycoprotein (Mr 200,000), which was shown previously to be associated with neurite and membrane preparations from cells with active Na+ channels, was decreased. Cell growth and viability were not affected. The nonphysiological isomer D-fucose or the addition of D-glucose in the same concentration did not inhibit differentiation. Vibrio cholerae neuraminidase, added to the cells prior to the stimulation of 86Rb efflux by veratridine and scorpion venom, was inhibitory. The implications of these findings, which suggest a key role for glycoproteins in at least a portion of the excitability process, are discussed.
A hematoporphyrin derivative (abbreviated in the literature as "HPD") has been used successfully for phototherapy of tumors in the clinic. The chemical nature of HPD, a complex mixture of porphyrins, is not fully understood. This study was designed to provide an explanation for the superior tumor-localizing ability of HPD. Chromatographic behavior, hydrophobicity, transport, binding, and photosensitizing capacity of different porphyrins were examined and compared. Biological studies were carried out using murine leukemia L1210 cells in vitro. The initial rate of porphyrin uptake was a function of drug hydrophobicity. The most hydrophobic components of HPD were therefore the most potent photosensitizers when irradiation followed a 10-min porphyrin-loading incubation. But these and other hydrophobic porphyrins were readily washed from cells by medium containing serum. Hydrophilic components of HPD were gradually accumulated by L1210 cells via a mode of binding not readily dissociated by washing and appear to be responsible for the preferential affinity of this product for neoplastic cells. A portion of the tightly bound porphyrin could not be dissociated by sodium dodecyl sulfate:polyacrylamide gel electrophoresis but remained bound to a low-molecular weight membrane component.
Explore the source record for details and available documents.
Thirteen patients were treated with a hydroxyurea -- 5-azacytidine combination in an attempt to show an increase in therapeutic efficacy of 5-azacytidine without increased bone marrow toxicity. Leukemic and nonleukemic patients were selected in order to compare the effect of a combination therapy on bone marrow. There was no clear-cut tumor response observed in evaluable patients. Overall activity of the combination, as judged by the onset of myelosuppression, appears to be higher than that of 5-azacytidine given alone.
Fucosyltransferase activity was measured in plasma samples obtained from patients with chronic granulocytic leukemia in different disease stages. Total enzyme activity was generally elevated in untreated and in stable disease; a marked further elevation was noted 30 to 60 days before development of blast crisis. Electrofocusing studies indicate the presence of three major enzymes. The level of enzyme which focused at pH 5.6 was elevated in untreated disease and rose markedly during blastic transformation. A second enzyme focused at pH 5.1 and appeared to be related to marrow erythroid turnover. A third enzyme with pI = 4.7 was elevated only during marrow regeneration which followed myelosuppressive therapy. These data suggest the enzyme with pI = 5.6 to be a specific marker in chronic granulocytic leukemia.