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Biomedical subjects

J Moan

Publications and source records attributed to J Moan.

At least 181 records · Page 10Linked to original sources
PubMed1985

Treatment of mouse carcinomas with intratumoral injections of hematoporphyrin derivative and red light.

Hairless mice with subcutaneously transplanted Lewis Lung carcinomas were used to study the effects of treatments with hematoporphyrin derivative (HPD) administered by intratumoral injection, followed by exposure to red light. A tumor cure rate of 70-90% was obtained following a single treatment. The therapeutic response increased with increasing HPD doses and light fluences. At a certain dose a plateau seemed to be reached, where further dose increase only gave a limited gain in treatment response. A narrow range seems to exist between beginning therapeutic response and frank necrotic destruction. The number of mice that died after treatment increased with increase in tumor size, and there was a correspondence between the time of death and the severity of the phototoxic reactions. The best therapeutic response was obtained when the irradiation was performed 1/2-1 h after injection, and with tumors less than 6-8 mm in diameter.

Animals↗
PubMed1984

Formation of metal complexes of tumor-localizing porphyrins.

Whereas the tumor localizer and photosensitizer hematoporphyrin derivative (Hpd) has its fluorescence emission maximum at 610-630 nm, several authors have reported that in aqueous solutions of hematoporphyrin (Hp) and Hpd, or in tumors after an injection of Hpd, a compound is formed which has its fluorescence emission maximum at 570-590 nm. This work (HPLC and fluorescence analysis) indicates that this peak is due to the formation of Zn-porphyrins either in vitro or in vivo. Cu- and Co-porphyrins may be formed as well, from traces of these metallic ions. In contrast to free porphyrins and Zn-porphyrins the latter complexes are non-fluorescent and do not act as photosensitizers.

Animals↗
PubMed1984

Tumor-localizing and photosensitizing properties of the main components of hematoporphyrin derivative.

Both 3H-labeled and unlabeled hematoporphyrin derivative (HPD) were analyzed by high-pressure liquid chromatography (HPLC) and gel permeation chromatography. Four main components were isolated by HPLC, and two were isolated by gel permeation chromatography. The tumor-localizing ability of each component was tested and compared to that of 67Ga and 3H2O by injection in mice bearing Lewis lung carcinoma. The photosensitizing abilities of the HPLC-separated components in vitro were also tested. Finally, porphyrin extracts of tumors from mice given HPD were analyzed by HPLC. The tumor-localizing ability of the components increased with decreasing polarity. While crude HPD localized in tumor tissue only to the same extent as did 3H2O, Component 7 was almost as effective as was 67Ga in localizing in the tumor. The cellular uptake of HPD components increased with decreasing polarity. In accordance with this, the low-polarity components were the most effective photosensitizers.

Animals↗
PubMed1983

Uptake of the components of hematoporphyrin derivative by cells and tumours.

The porphyrin content of cells labelled with hematoporhyrin derivative (Hpd) and tumours of mice injected with Hpd was analysed by means of high pressure liquid chromatography (HPLC). The components of Hpd may be classified in 3 groups: (A) Components with a high fluorescence quantum yield and with sharp peaks in the HPLC chromatogram. These are monomers. (B) Components with a lower fluorescence quantum yield and with sharp peaks in the HPLC chromatogram. These are probably dimers or oligomers. (C) Components with a low fluorescence quantum yield, with a short retention time on a P-10 column and with a broad and unresolved peak in the HPLC chromatogram. These are probably large aggregates. Components of group A are rapidly accumulated by cells but are easily removed by washing the cells with medium containing serum. Porphyrins of group B are significantly more concentrated by cells in vitro than porphyrins of group A and B and accumulate over a time interval of about 18 h. Porphyrins of group B gradually migrate to sites in the cells where they are more strongly retained. Tumors in mice behave differently from tumor cells in vitro since they mainly contain porphyrins of group C after an i.p. injection of Hpd in the mice.

Animals↗
PubMed1983

Retention and photodynamic effects of haematoporphyrin derivative in cells after prolonged cultivation in the presence of porphyrin.

Photoradiation therapy of cancer in the presence of haematoporphyrin derivative is based on a retention of porphyrin in malignant tissue. After long term incubation of NHIK 3025 cells in the presence of 25 microgram ml-1 haematoporphyrin derivative, one fraction is easily removed from the cells by washing with a serum-rich medium. Another fraction remains bound to the cells for a prolonged time. The former does not contribute to the photosensitivity of the cells while the latter, the tightly-bound component, results in a photosensitivity proportional to the cellular contents of porphyrin. Transformed cells are shown to be slightly more sensitive and to retain 25-50% more haematoporphyrin derivative than non-transformed cells. Cytological effects of light absorbed by the tightly-bound component have been studied. The growth of treated cells is similar to that of control cells after a dose-dependent post irradiation lag period. A relatively slow leakage of lactate dehydrogenase (LDH) out of the cells takes place after treatment. The treatment induces a significant increase in the frequency of sister chromatid exchanges (SCE). We conclude that photoactivation of the tightly-bound fraction of haematoporphyrin derivative induces less damage to the outer cell membrane and probably more intracellular damage than irradiation of cells after a short period in contact with the derivative.

Animals↗
PubMed1983

Combined electron radiation and hyperthermia. Repair of DNA strand breaks in NHIK 3025 cells irradiated and incubated at 37, 42.5, or 45 degrees C.

Induction of DNA strand breaks by a short electron pulse (18.5 Gy) and the subsequent strand-break rejoining were investigated at hyperthermia (42.5 and 45 degrees C) and at 37 degrees C during irradiation and repair. The cells were irradiated immediately after 2.5 min equilibration (i.e., from 37 to 42.5 or 45 degrees C) to investigate the effect of short-duration hyperthermia on radiation damage and subsequent repair. Due to a high radiation dose rate and a rapid lysis technique, the cells could be kept at the actual temperature during irradiation and repair, and the strand-break frequency could be measured only seconds after irradiation. At all temperatures, a constant or possible increase in the initial number of breaks was observed during the first 7 sec after the electron pulse. At 37 degrees C, strand-break rejoining was nearly complete within 1 hr. Hyperthermia at 42.5 degrees C had only minor influence on the net rate of strand-break rejoining. At 45 degrees C, 50% of the breaks remained after 1 hr. Subsequent incubation for 23 hr at 37 degrees C reduced by half the number of breaks remaining at 1 hr in irradiated samples. Unirradiated samples exposed to the same heat treatment showed a significant increase in the number of DNA strand breaks. Thus, heat treatment at 45 degrees C may lead to a combined effect of reduced rejoining capacity and formation of breaks after the electron pulse which in turn may be responsible for increased cell death when both modalities are employed.

Animals↗
PubMed1982

The main photosensitizing components of hematoporphyrin derivative.

Commercial hematoporphyrin (Hp) and the tumor-localizing and photosensitizing agent hematoporphyrin derivative (Hpd) were analysed by means of high pressure lipid chromatography (HPLC). Furthermore, their efficiencies in sensitizing the photoinactivation of human cells in vitro were compared. The comparison showed that the least polar components of Hpd played the major role in this sensitization. In Hpd solutions used for injection in photochemotherapeutic treatment of cancer, these active components seem to be present as aggregates.

Cell Line↗
PubMed1982

Photodynamic action and chromosomal damage: a comparison of haematoporphyrin derivative (HpD) and light with X-irradiation.

Chromosomal aberrations (CA) are induced in human cells (NHIK 3025) in vitro when exposed to X-rays and to haematoporphyrin derivative (HpD) plus light. At the 0 . 1 survival level X-rays induce about 10 times more breaks per chromosome than the photodynamic treatment. There is some evidence for non-random distribution of the CA induced by HpD plus light; i.e. they seem to be localized at the centromeric and telomeric regions. Such non-random distribution of CA could be explained if centromeric and telomeric chromatin were associated with the inner nuclear membrane.

Carcinoma in Situ↗
PubMed1982

Porphyrin-sensitized photoinactivation of human cells in vitro.

NHIK 3025 cells derived from a carcinoma in situ were exposed to hematoporphyrin derivative (Hpd) and light and examined by light microscopy, freeze-etching, scanning, and transmission electron microscopy. The first morphologic changes observed were shrinkage of mitochondria and formation of vesicles on the cell membrane. Furthermore, increased membrane permeability led to accumulation of Hpd and cellular swelling, with a concomitant reduction in the number and size of the microvilli. Some of the vesicles seemed to originate from microvilli. The freeze-etching appearance of the membranes of the majority of the cells was unaltered by treatment with Hpd and light. However, in some cases clustering of membrane particles was observed. At low doses membrane vesiculation and cell swelling were reversed within a few hours after treatment, indicating that repair processes were operative.

Carcinoma in Situ↗
PubMed1982

Release of lysosomal enzymes and lactate dehydrogenase due to hematoporphyrin derivative and light irradiation of NHIK 3025 cells in vitro.

NHIK 3025 cells in monolayer cultures were irradiated with near ultraviolet light in the presence of hematoporphyrin derivative (HPD). The release of lysosomal enzymes and the cytosol marker enzyme lactate dehydrogenase to the culture medium was determined 1, 3, 6 and 24 hours after irradiation. The enzyme activities of the cell pellet were investigated 24 hours after irradiating the cells. After exposure of HPD-labelled cells to light doses causing no cell inactivation, the leakage of enzymes was slightly inhibited in the first 6 hours followed by a period between 6 and 24 hours when the cells released the same amount or slightly more enzymes than the control. The enzyme activities of cell pellets made 24 hours after exposure were 40-75% of control values due to either a small inhibition of cellular enzyme activity or of inhibited cell growth by this dose. A higher light dose inactivating 80-90% of the cells, caused a rapid release of both lysosomal and cytosol enzymes. The cell pellets contained very little of the enzymes 24 hours after treatment and especially free intracellular enzymes had been released with high efficiency. Leupeptin, a lysosomal protease inhibitor, did not protect the cells from inactivation. We conclude that the release of lysosomal enzymes after porphyrins and light is of little significance in terms of cell killing.

Acetylglucosaminidase↗