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Biomedical subjects

J F Evensen

Publications and source records attributed to J F Evensen.

33 records · Page 2Linked to original sources

Localization of fluorescent Photofrin II and aluminum phthalocyanine tetrasulfonate in transplanted human malignant tumor LOX and normal tissues of nude mice using highly light-sensitive video intensification microscopy.

A comparative kinetic observation of the in vivo biolocalization of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AIPCS4) in a transplanted human malignant tumor LOX and in normal tissues of nude mice has been made by means of highly light-sensitive video intensification microscopy at various intervals after i.p. administration. In the human tumor LOX, transplanted to athymic nude mice, fluorescence of P-II was observed on the membrane and in the cytoplasm of tumor cells, and in the stroma 4-48 hr post-injection. From 72 hr post-injection almost all fluorescing P-II had disappeared from the membrane of the tumor cells while strong fluorescence was still found in the stroma. AIPCS4 fluorescence was seen mainly in tumorous stroma with none detected in the tumor cells. Almost no fluorescence was found in the tumorous stroma 24 hr after injection. In most normal tissues observed, P-II was eliminated at a much slower rate than AIPCS4, but the in vivo biolocalization of the 2 drugs was similar. They were observed primarily where collagenous proteins are normally found, i.e. basal lamina, collagenous connective tissue, and in keratinized epithelium, renal epithelium, mononuclear phagocyte system and on the membrane of muscular cells. In addition, AIPCS4 had a strong affinity for the bronchiogenic epithelium. In the skin, P-II was distributed in keratinized epithelium, hair, hair follicles and their accessory, collagenous connective tissue of dermis, whereas AIPCS4 was present only in hair and collagenous connective tissue of dermis. No fluorescence of P-II or of AIPCS4 was found in the skin epidermis, nor in the transitional epithelium of the bladder mucosa.

Animals↗

Hematoporphyrin diethers--V. Plasma protein binding and photosensitizing efficiency.

1. Binding of added hematoporphyrin (HP) ethers to human plasma proteins and lipoproteins has been investigated by ultracentrifugation. 2. The binding to low density lipoproteins (LDL) has been discussed in terms of photosensitized tumor growth delay of tumors and HPLC-retention time, i.e. degree of polarity. 3. The LDL-binding data show a uniform relationship to sensitizing efficiency and degree of polarity, the only exception being HP-diamyl ether. No such uniform relationship exists for less related dyes, such as HP, tetraphenylporphyrin tetrasulfonate and HP-dimethyl ether.

Animals↗

Preparation and photosensitizing properties of hematoporphyrin ethers.

Hematoporphyrin ethers having acyl or aryl substituents in the 2 and 4 positions of the porphyrin ring have been synthesized, starting from protoporphyrin HBr adduct, and tested for photosensitizing efficiency on cells in vitro and transplanted tumors in mice. In general, they resemble the tumor localizing fraction of hematoporphyrin derivative (Hpd). Cellular uptake and retention runs parallel with the degree of their non-polarity and in vitro sensitizing efficiencies are up to ten times that of Hpd or Photofrin II (P II). They have high quantum yields for inactivation of cells and also relatively low in vivo skin/tumor concentration ratios.

Animals↗

Testicular seminoma: histological findings and their prognostic significance for stage II disease.

Risk factors, their interrelationship, and prognostic relevance for seminoma stage II disease have been examined. The size of the primary tumor was significantly correlated with the pT category, as was the presence of tumor invasion of small vessels. The pT category was correlated neither with clinical substage nor relapse rate. There was a poorer 3-year survival for anaplastic seminomas as compared to that of classical seminomas; the difference was not significant. The 5-year survival for seminomas rich in lymphocytes was better than those of poor lymphocytic infiltration, but this difference also was not significant. No difference in survival or relapse rate was found between HCG-producing and HCG-nonproducing seminomas.

Chorionic Gonadotropin↗

A comparison of different photosensitizing dyes with respect to uptake C3H-tumors and tissues of mice.

Nine dyes, all potential sensitizers for photodynamic cancer therapy (PDT), were injected in mice with C3H mammary carcinomas. Twenty-four hours later the animals were sacrificed and the dye concentrations in tumors and 9 other tissues were measured by means of spectrofluorimetry. The 9 dyes were: Photofrin II (PII), hematoporphyrin (HP)-di-hexyl-ether, PSD-007 (a sensitizer used in clinical trials in China), tetraphenyl porphine tetrasulfonate (TPPS4), tetra(3-hydroxy phenyl)porphyrin (3THPP), aluminium phthalocyanine tetrasulfonate (AlPCTS), aluminium phthalocyanine (AlPC), chlorin e6 (Chl e6) and merocyanine 540 (MC 540). The porphyrin precursor delta-aminolevulinic acid was also tested and found to induce porphyrin fluorescence in tumors and some other tissues. The best tumorlocalizer of those tested was 3THPP. This drug also showed a favorable tissue distribution. The following dyes showed lower skin/tumor concentration ratios than PII (the most widely used dye for PDT): Chl e6, PSD-007, HP-di-hexyl-ether and 3THPP. Low brain/tumor ratios were found for: PSD-007, HP-di-hexyl-ether, 3THPP, TPPS4 and AlPCTS.

Animals↗

Photodynamic therapy of C3H mouse mammary carcinoma with haematoporphyrin di-ethers as sensitizers.

Haematoporphyrin di-ethers were synthesized and tested as sensitizers for photodynamic therapy of C3H/Tif mammary tumours in mice. Growth curves of the tumours were determined by measuring the tumour volume. The animals were given 25 mg porphyrins kg-1 body weight i.p. and 24 h later exposed to 135 J cm-2 of 630 nm light at a fluence rate of 150 mW cm-2. The sensitizing efficiency of the ethers was measured in terms of the increase in growth time of the treated tumours, as compared with that of untreated controls, needed to reach a volume 5 times larger than that at the time of the treatment. This sensitizing efficiency increased with decreasing polarity, i.e. in the order di-methyl ether, di-propyl ether, dibutyl ether and di-amyl ether. Haematoporphyrin di-amyl ether was more efficient than haematoporphyrin derivative and insignificantly less efficient than photofrin II (DHE). This was true for sensitization of both tumours and normal tissue.

Animals↗

Toxic and phototoxic effects of tetraphenylporphinesulphonate and haematoporphyrin derivative in vitro.

The toxic and phototoxic effects of tetraphenylporphinesulphonate (TPPS4) and haematoporphyrin derivative (HpD) have been examined in vitro. TPPS4 was found to have less dark toxicity to the cells than HpD as measured by inhibition of cell multiplication and colony formation at comparable extracellular concentrations. TPPS4 was also less effective than was HpD in photoinactivating NHIK 3025 cells by more than a factor 2 which should be expected on the basis of cellular uptake. Spectrofluorometric data suggest that HpD in cells interacts more with lipids than TPPS4. This might explain the large photosensitizing effect of HpD compared to TPPS4 since the lifetime of singlet oxygen is about a factor of 10 longer in a lipid environment than in an aqueous environment. The uptake of TPPS4 and HpD by cancer cells in vitro does not correlate with previous in vivo data, indicating retention of TPPS4 in the tumour stroma. This makes in vitro/in vivo extrapolation difficult with regard to the use of TPPS4 as an agent for photodynamic therapy.

Biological Transport↗

Testicular seminoma: analysis of treatment and failure for stage II disease.

Seventy-three patients with seminoma testis stage II have been retrospectively analyzed with regard to prognostic factors and value of prophylactic mediastinal irradiation and chemotherapy. Although survival differences were seen between stage IIa, IIb and IIc, these were not statistically significant. Neither was there a significant difference between IIc patients with tumors greater than 10 cm and less than 10 cm in diameter. The incidence of HCG-producing seminomas in the present series was 16%. No significant difference in survival nor relapse rate was found between HCG-producing and HCG-non-producing seminomas. Prophylactic mediastinal irradiation did not influence the survival nor the relapse rate and may therefore be omitted. In the present series there was no significant improvement neither in relapse rate nor survival in patients receiving pre-irradiation chemotherapy. However, the total number of patients is small and optimal pre-irradiation chemotherapy still have to be defined.

Adult↗

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↗

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↗

Non-steroidal anti-inflammatory drugs and the risk of oral cancer: a nested case-control study.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) seem to prevent several types of cancer, but could increase the risk of cardiovascular complications. We investigated whether use of NSAIDs was associated with a change in the incidence of oral cancer or overall or cardiovascular mortality. METHODS: We undertook a nested case-control study to analyse data from a population-based database (Cohort of Norway; CONOR), which consisted of prospectively obtained health data from all regions of Norway. People with oral cancer were identified from the 9241 individuals in CONOR who were at increased risk of oral cancer because of heavy smoking (15 pack-years), and matched controls were selected from the remaining heavy smokers (who did not have cancer). FINDINGS: We identified and analysed 454 (5%) people with oral cancer (279 men, 175 women, mean [SD] age at diagnosis 63.3 [13.2] years) and 454 matched controls (n=908); 263 (29%) had used NSAIDs, 83 (9%) had used paracetamol (for a minimum of 6 months), and 562 (62%) had used neither drug. NSAID use (but not paracetamol use) was associated with a reduced risk of oral cancer (including in active smokers; hazard ratio 0.47, 95% CI 0.37-0.60, p<0.0001). Smoking cessation also lowered the risk of oral cancer (0.41, 0.32-0.52, p<0.0001). Additionally, long-term use of NSAIDs (but not paracetamol) was associated with an increased risk of cardiovascular-disease-related death (2.06, 1.34-3.18, p=0.001). NSAID use did not significantly reduce overall mortality (p=0.17). INTERPRETATION: Long-term use of NSAIDs is associated with a reduced incidence of oral cancer (including in active smokers), but also with an increased risk of death due to cardiovascular disease. These findings highlight the need for a careful risk-benefit analysis when the long-term use of NSAIDs is considered.

Acetaminophen↗