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Biomedical subjects

T Patrice

Publications and source records attributed to T Patrice.

At least 37 records · Page 2Linked to original sources
PubMed1995

Correlation between meta(tetrahydroxyphenyl)chlorin (m-THPC) biodistribution and photodynamic effects in mice.

Analysis of sensitizer kinetics is essential for the performance of light irradiation when tumour concentration and tumour-to-normal tissue ratios are optimal. In this study nude mice were grafted with human adenocarcinoma 15 days before meta(tetrahydroxyphenyl)chlorin (m-THPC) intra-peritoneal (IP) injection. Fluorescence was recorded through an optic fibre spectrofluorometer at 650 (the most intense) and 714 nm, with intensity being proportional to injected dose. In tumour, skin and muscle the maximum fluorescence was obtained with 1.6 mg kg-1 72 h after injection (44 counts per second). Tumour-to-skin and tumour-to-muscle ratios obtained by high performance liquid chromatography (HPLC) analysis and spectrofluorometric measurements decreased between 12 and 72 h (from 15 to 1.5), indicating that tumour selectivity decreases with time. This contrast between selectivity and fluorescence levels was also observed with photodynamic therapy (PDT) results, for which no differences were observed when 10 J cm-2 were delivered at 100 or 200 mW. PDT results were better 24 h after drug administration than at 72 h. Tumour growth decrease (-40%) was found when 1.6 mg kg-1 were injected 24 h before irradiation. For other groups a slower increase (12% vs. 23%) was noted in the first few days after PDT. The paradoxal correlation between fluorometric or HPLC measurements and PDT effects suggests that m-THPC localizes differently with time in tumour components.

Adenocarcinoma↗
PubMed1995

HepG2 human hepatocarcinoma cells: an experimental model for photosensitization by endogenous porphyrins.

Endogenous protoporphyrin IX (PpIX) synthesis after delta-aminolaevulinic acid (ALA) administration occurs in cancer cells in vivo; PpIX, which has a short half-life, may thus constitute a good alternative to haematoporphyrin derivative (HPD) (or Photofrin). This study assesses the ability of the human hepatocarcinoma cell line HepG2 to synthesize PpIX in vitro from exogenous ALA, and compares ALA-induced toxicity and phototoxicity with the photodynamic therapy (PDT) effects of HPD on this cell line. ALA induced a dose-dependent dark toxicity, with 79% and 66% cell survival for 50 and 100 micrograms ml-1 ALA respectively after 3 h incubation; the same treatment, followed by laser irradiation (lambda = 632 nm, 25 J cm-2), induced a dose-dependent phototoxicity, with 54% and 19% cell survival 24 h after PDT. Whatever the incubation time with ALA, a 3 h delay before light exposure was found to be optimal to reach a maximum phototoxicity. HPD induced a slight dose-dependent toxicity in HepG2 cells and a dose- and time-dependent phototoxicity ten times greater than that of ALA-PpIX PDT. After 3 h incubation of 2.5 and 5 micrograms ml-1 HPD, followed by laser irradiation (lambda = 632 nm, 25 J cm-2), cell survival was 59% and 24% respectively at 24 h. Photoproducts induced by light irradiation of porphyrins absorb light in the red spectral region at longer wavelengths than the original porphyrins. The possible enhancement of PDT effects after HepG2 cell incubation with ALA or HPD was investigated by irradiating cells successively with red light (lambda = 632 nm) and light (lambda = 650 nm)(ABSTRACT TRUNCATED AT 250 WORDS)

Aminolevulinic Acid↗
PubMed1994

DNA or cell kinetics flow cytometry analysis of 33 small gastrointestinal cancers treated by photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) mediated by hematoporphyrin derivative (HPD) is a new treatment for cancers of small volume undergoing Phase II or III clinical trials in various medical fields. However, there is a lack of prognostic criteria of efficacy as in other cancer treatment. METHODS: Cell DNA content or cell kinetics throughout the cell cycle were analyzed by flow cytometry and propidium iodide staining before and after HPD-PDT in 33 patients with Tis or T1 cancers of the gastrointestinal tract. The authors compared results in near-diploid cancers with those obtained in normal corresponding tissue. RESULTS: Complete local tumor destruction and negative histologic findings (complete response [CR]) were observed in 17 of 33 patients during a period averaging 15.7 months. Flow cytometry DNA analysis was feasible in 32 patients. Aneuploidy, found in 15 of the 32 indicated a poor prognosis because 5 of 15 patients with aneuploid tumors were classified as having CR, compared with 12 of 17 patients with near-diploid tumors (P < 0.05). Changes in ploidy after PDT in 11 patients consisted of a reduction in the number of aneuploid peaks in 8 patients and the appearance of one aneuploid peak in 3 patients. Percentages of cells in SG2M phase in near-diploid tumors differed from those observed in control subjects for adenocarcinomas, and there was no significant decrease after HPD-PDT. There was no correlation between the decrease of SG2M cells and the response to HPD-PDT. CONCLUSION: Results obtained with PDT in this series of patients confirm previously published findings. Changes occurring in the ploidy of PDT-treated patients demonstrate that PDT acts directly on cancer cells in humans and not only on tumor vasculature. However, response to PDT varies from one cell population to another. The appearance of aneuploid populations after PDT suggests that destruction of sensitive cell populations allows the growth of aneuploid clones that initially are not detectable by flow cytometry.

Adenocarcinoma↗
PubMed1994

Experimental model of liver metastases: adhesion and growth of cells on contact with endothelial or hepatocyte cell monolayer cultures.

In a rat colon carcinoma model (DHD/K 12-PROb), two varieties of cells were selected after in vivo passaging: PROb h2, representing a liver-specific variant and PROb Mp1, representing a lung metastatic variant and producing liver and lung metastases after intracecal injection (one out of four). The study of the adhesion and the growth of cells in vitro for contact hepatocytes and/or endothelial cells gave the following results: (1) except for PROb Mp1, tumor cell growth was independent of the cell support; (2) adhesion of PROb Mp1 to endothelial cells was lower between 30 and 120 min, whereas adhesion of PROb h2 to hepatocytes was greater and durable after 60 min (P < or = 0.05). These results suggest that the formation of liver metastases in a dynamic process and that tumor cells have a great ability to adhere to hepatocytes. Improved by serial passaging in vivo, our intracecal model might be useful for studying many aspects of the pathogenesis of colon cancer metastasis, while concurrent in vitro studies of the adhesion and growth ability of cells might be a useful indicator for assessing the in vivo behavior.

Animals↗
PubMed1994

Modulation of colonic cancer cell adhesiveness by haematoporphyrin derivative photodynamic therapy.

Haematoporphyrin derivative photodynamic therapy (HPD-PDT) induces damage of plasma membranes and other cellular targets. This damage could modify the adhesiveness of cancer cells, which is an important parameter in cancer metastasis. We studied the effect of HPD alone and HPD incubation followed by argon laser light on the adhesiveness of progressive (PROb) or regressive (REGb) cancer cells of the same colonic origin. Adhesiveness was studied on plastic or endothelial cell monolayers (ECMs). In the absence of treatment, both PROb and REGb cells adhered better on plastic than on ECs. HPD alone and HPD-PDT induced toxicity proportional to the HPD dose. HPD-PDT increased the adhesiveness rate of both cell lines on plastic and decreased adhesiveness to ECs. HPD-PDT of ECMs increased adhesiveness but only for HPD doses giving at least 50% cell death. HPD alone and HPD-PDT of culture media led to an insignificant decrease in the cell adhesiveness to ECMs. As cells which are more metastatic are also more adherent, a decreased adhesiveness to ECMs after HPD-PDT suggests that PDT is a safe treatment considering metastasis.

Animals↗
PubMed1994

Photophysical and photobiological activities of a porphyrin peptide fraction derived from haemoglobin.

In a previous study, we described the preparation of a porphyrin peptide hydrolysate from haemoglobin, its isolation and its analysis by high performance liquid chromatography (HPLC) and fast atom bombardment (FAB) mass spectrometry. The purpose of the present paper is to test the photosensitizing activity of this fraction. We determined the singlet oxygen quantum yield (phi delta) in order to quantify the efficiency of the porphyrin peptide fraction. The quantum yield is about phi(1O2)=0.06. An analysis of the phototoxic effect on tumour cells in culture was performed and compared with haematoporphyrin derivative (HpD), the only photosensitizer in clinical use at present. The phototoxicity of the porphyrin peptide fraction is weaker than that of HpD. However, for a porphyrin dose of 50 micrograms ml-1, the difference in phototoxicity is low, and in the absence of irradiation porphyrin peptides are less toxic than HpD. These results suggest that porphyrin peptides could be potent photosensitizers; moreover, they are of great interest since they allow the solubilization of hydrophobic porphyrins and could be applied in the future as insoluble photosensitizer carriers.

Cell Line↗
PubMed1994

Malondialdehyde dosimetry in laser-irradiated tissues sensitized by hematoporphyrin derivative.

Photodynamic therapy (PDT) is based on the selective retention of a photosensitizer (hematoporphyrin derivative [HPD]) by tumor tissue and the subsequent irradiation of this tissue with light. Unsaturated phospholipids are important targets of membrane photodamage, and malondialdehyde (MDA), an ultimate marker of lipid peroxidation, can easily be measured by the fluorometric thiobarbituric acid (TBA) assay. To determine whether MDA content represents a reference for PDT intensity, tissue content in 7-week-old male nude mice was studied on biopsy samples after PDT (5 mg/kg HPD injected intravenously 24 hr before irradiation at 632 nm) with or without intraperitoneal injection of WR-2721 40 min before treatment. The FeCl3 method requiring only 15 min of incubation in a 95 degrees C waterbath proved most effective compared with the method involving phosphotungstic acid or the MDA-TBA determination using a commercially available kit. Whatever the method used, the best results were found using a 60-min interval between treatment and freezing. MDA concentration in HPD-PDT-treated samples was significantly higher than in HPD-tested controls (P < .01) and increased at laser irradiation doses ranging from 0 to 50 J/cm2. Administration of WR-2721 intraperitoneally significantly reduced MDA concentration (from 70% to 38%). A maximal effect was obtained with 100 mg/kg for brain (-70%) and 200 mg/kg for muscle (-47%). Higher doses produced no additional changes. The MDA assay is a simple tool for indirect evaluation of PDT, and WR-2721 can decrease MDA content in normal tissue, suggesting the possibility of good protection for normal tissue during PDT.

Amifostine↗
PubMed1992

Photodynamic treatment of normal endothelial cells or glioma cells in vitro.

Photodynamic therapy is based on the interaction of a sensitizer (hematoporphyrin derivative) selectively retained by tumor cells, which becomes toxic after light exposure. We studied the influence of exogenous prostaglandins and indomethacin on photodynamic therapy of normal human endothelial cells and glioma cells. Although differing in origin and kinetic properties, endothelial cells exhibited photodynamic therapy sensitivity quite comparable to that of C6 cells. However, in contrast to studies performed using radiotherapy, exogenous prostaglandins decreased rather than protected the surviving fraction of both cell types treated by photodynamic therapy. Indomethacin, a potent inhibitor of endogenous prostaglandin synthesis, increased the surviving fraction of C6 glioma cells but not that of endothelial cells. Exogenous or endogenous prostaglandins seem to influence in vitro photodynamic therapy in a different way than does radiotherapy.

Animals↗
PubMed1992

Effects of high glucose concentration on survival and respiration of human endothelial cells.

To determine whether or not endothelial cell survival was decreased after incubation with high glucose concentrations in culture media, we studied the influence of D-glucose or L-glucose (a non-metabolizable stereoisomer of D-glucose) on cell survival using the trypan-blue exclusion test. Simultaneously, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide) assay was used to measure both the mitochondrial respiratory chain activity and cell viability. Respiratory chain activity per cell increased when D-glucose concentrations rose but at the same time trypan-blue excluded cells were decreased. Comparison with data in the literature showed that the MTT assay was not reliable for studies involving endothelial cell survival when glucose reduction was affected on these cells. It seems important to check MTT assay reliability carefully when it is used for drugs affecting glucose metabolism, or with other cell types.

Cell Survival↗
PubMed1991

Photosensitization of L1210 leukaemic cells by argon laser irradiation after incubation with haematoporphyrin derivative and rhodamine 123.

The selectivity and efficacy of photodynamic therapy (PDT) may be improved by the combined use of photosensitizers in a similar manner to the combined use of drugs in cancer chemotherapy. Two photosensitizers (haematoporphyrin derivative (HPD) and rhodamine 123 (Rh-123) were analysed which can be irradiated at the same wavelength (514 nm), are preferentially taken up by tumour tissue and are not specific for the same target (membrane for HPD, mitochondria for Rh-123). The analysis of the phototoxic effects in surviving fractions showed a dependence on dose for both products and a dependence on incubation time for HPD but not Rh-123. The lethal dose for 50% cell death (LD50) for HPD increased from 25 to 56 J cm-2 when the HPD dose was reduced from 2.5 to 1 micrograms ml-1 for the same incubation time. When the incubation time was increased from 15 to 45 min, the surviving fraction decreased by 37% and 17% for doses of 1 and 2.5 micrograms ml-1 respectively. For low doses (0.5 and 1 microgram ml-1), the toxicity of the two photosensitizers added simultaneously was weaker than for Rh-123 alone, whereas for high doses (2.5 micrograms ml-1) the surviving fraction was less than that obtained with Rh-123 alone. These results were compared with the light energy absorbed, the quantum yield of singlet oxygen and Rh-123 uptake as determined by flow cytometry analysis.

Animals↗
PubMed1991

[Effect of gastrin and enprostil, a PGE2 analog, on colonic cancerous cell growth].

The effects of gastrin (G-17), proglumide (a gastrin receptor antagonist), and enprostil (a synthetic analog of prostaglandin E2) used alone or in association were studied in colonic cancer Prob and Regb cell growth. The Prob (progressive in BD IX rats) and Regb (regressive) cell lines were cloned from a single chemically-induced rat colonic cancer. After a serum-free period corresponding to one doubling cell time, cells were incubated with 100 to 1,200 pM G-17, 40 or 80 mM proglumide, and 2.5 to 5 micrograms/ml enprostil for 8 h. Cell growth was measured 48 h later by colorimetric MTT assay. Two and four hundred pM G-17 gave a growth stimulation of 17.4 percent and 31 percent for Prob cells respectively or 35.5 percent and 49 percent for Regb cells. Growth stimulation was found to be statistically different (P less than 0.01) for Prob and Regb cells. Proglumide partially inhibited this growth stimulation whereas enprostil inhibited in totally. These results suggest that growth of some colonic cancer cell lines may be G-17 dependent. However the intensity of cell-growth stimulation depends on the level of cell malignancy or differentiation in a single tumor.

Adenocarcinoma↗
PubMed1990

Endoscopic photodynamic therapy with hematoporphyrin derivative for primary treatment of gastrointestinal neoplasms in inoperable patients.

Endoscopic photodynamic therapy with hematoporphyrin derivative was used in the primary treatment of 54 patients with inoperable gastrointestinal neoplasms. Patients were divided into three groups including 24 with esophageal squamous cell carcinoma, 14 with adenocarcinoma of the stomach or lower third of the esophagus, and 16 with rectosigmoid adenocarcinoma. After infusion of 2.5-5.0 mg hematoporphyrin derivative/kg of body weight, lesions were photoradiated using an argon dye laser with power set at 300-400 mW for 5 min/site. During a follow-up period averaging 14.5 months (range 1-33 months), complete local tumor destruction and negative histology were observed in 24 of 54 cases. The mean recurrence-free period varied from 13.8 to 17.4 months according to groups. Fifteen patients remain alive and disease-free. The results of this open pilot study suggest the potential efficacy of photodynamic therapy as curative treatment for selected cases of inoperable gastrointestinal cancers, possibly in association with locoregional radiotherapy.

Adenocarcinoma↗
PubMed1990

Endoscopic photodynamic therapy with haematoporphyrin derivative in gastroenterology.

Endoscopic photodynamic therapy (PDT) with haematoporphyrin derivative was used in the primary treatment of 69 patients with inoperable gastrointestinal neoplasms. Patients were divided into three groups: 31 with oesophageal squamous cell carcinoma, 17 with adenocarcinoma of the stomach or lower third of the oesophagus and 21 with rectosigmoid adenocarcinoma. After infusion of 2.5-5.0 mg haematoporphyrin derivative per kilogram of body weight, lesions were irradiated using an argon dye laser (632 nm). During a follow-up period averaging 20 months (27.9 months for 35 surviving patients), complete local tumour destruction and negative histology were observed in 32 out of 69 cases. Flow-cytometric analysis of DNA content before and after PDT suggests that a clonal selection occurs in some cases of treatment failure. The results of this open pilot study suggest the potential efficacy of PDT as a curative treatment for selected cases of inoperable gastrointestinal cancers.

Adenocarcinoma↗
PubMed1990

The protection of hemopoietic mice progenitors by WR-2721 during photodynamic therapy.

Photodynamic therapy is a new concept for in vitro evaluation of bone marrow clearance in leukemia. This treatment eliminates 99.9999% of leukemic cells, but under the same conditions over 50% of normal bone marrow cells are damaged. WR-2721, a thiol compound, is reported to except a protective effect for bone marrow against radiation therapy. This study analyzed the protective effect of WR-2721 during photodynamic therapy with hematoporphyrin derivative. Mice hemopoietic cells were exposed to laser light after sensitization by hematoporphyrin, with or without WR-2721 at 3 dose levels (250, 500, 750 mg/kg). The efficacy of protection was evaluated by GM-CFU assay in collagen gel medium. Results showed significant protection at 25 and 50 j/cm2 (p less than 0.05), but at 75 j/cm2 irradiation only the 750 mg/kg dosage remained protective. The protective factor of WR-2721 is 1.65 (95% confidence interval: 1.38-1.99) WR-2721 is protective against photodynamic lesions but this protection is diminished by increased irradiation energy. The best results are obtained with a dose of 750 mg/kg though this appears to be toxic. Further studies are needed to evaluate the action of WR-2721 on leukemic cells before the use of WR-2721 in bone marrow clearance.

Amifostine↗