Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Meta-tetrahydroxyphenylchlorin (m-THPC) and 5-aminolaevulinic acid (5-ALA) are two second-generation photosensitizers which are currently under investigation for photodynamic therapy (PDT) and photodynamic diagnosis (PDD). So far, the experience with these photosensitizers for use within brain tumours is limited. We examined the distribution and retention of 14C-labelled m-THPC and [14C]5-ALA in the rat C6 glioma brain tumour model. After intraperitoneal injection of m-THPC (71,909 d.p.m. microl(-1); 0.16 mg ml(-1) m-THPC; 0.3 mg kg(-1)), the following activities were found after 36 h: brain tumour 223,664 d.p.m. g(-1), brain contralateral to the tumour side 2567 d.p.m. g(-1), liver 369,959 d.p.m. g(-1) and skin 55,197 d.p.m. g(-1); 100,000 d.p.m. corresponding to 0.22 microg of m-THPC. After 7 days, the concentration of m-THPC decreased to 76,277 d.p.m. g(-1) in tumour and 635 d.p.m. g(-1) in brain. The radioactivity after intravenous administration of [14C]5-ALA (23,079 d.p.m. microl(-1); 40 mg ml(-1); 120 mg kg(-1)) increased within 15 min (59,634 d.p.m. g(-1) in tumour, 17,427 d.p.m. g(-1) in brain); after 8 h only a small amount (3653 d.p.m. g(-1) in tumour) remained. Brain adjacent to the tumour was also found to have a higher uptake of 5-ALA. This study provides basic information for the use of m-THPC and 5-ALA in brain tumours. Because of the different pharmacokinetic and toxicological profile, we recommend m-THPC for PDT and 5-ALA for PDD. Clinical trials now have to prove the superior phototoxic properties of these second-generation photosensitizers.
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PMID:Uptake and kinetics of 14C-labelled meta-tetrahydroxyphenylchlorin and 5-aminolaevulinic acid in the C6 rat glioma model. 974 91

This paper reports the synthesis of a new diphenylchlorin photosensitizer, 2,3-dihydro-5,15-di(3,5-dihydroxyphenyl)porphyrin (SIM01). The photodynamic properties, cell uptake and localization of SIM01 were compared with those of structurally related meso-tetra(hydroxyphenyl)chlorin (m-THPC). In vitro studies were conducted on rat glioma cells (C6) and human adenocarcinoma (HT-29), and in vivo studies on human colon adenocarcinoma cells (HT-29) and human prostate adenocarcinoma cells (PC3). Both dyes showed an absorption maximum at around 650 nm, with a molar extinction coefficient of 13017 M(-1) cm(-1) for SIM01 and 22718 M(-1) cm(-1) for m-THPC. Their capacity to generate singlet oxygen was identical, but differences in partition coefficients indicated that SIM01 was slightly more hydrophilic. In vitro, SIM01 was slightly more phototoxic than m-THPC for C6 cells (4.8 vs. 6.8 microg ml(-1)). However, phototoxicities were nearly identical for HT29 cells (0.45 microg ml(-1) for 5 h incubation followed by 300 mW, 20 J cm(-2)). Pharmacokinetics in vivo in mice, as determined by fibre spectrofluorimetry, showed that the SIM01 fluorescence signal in the tumor was maximal between 6 and 12 h after injection, as compared to 72 h for m-THPC. With a 2 mg kg(-1) dye dose and laser irradiation at 300 J cm(-2) (650 nm, 300 mW), the optimal PDT response occurred when the interval between injection and irradiation was 6 h for SIM01 and 24 h for m-THPC. For SIM01 with 5 mg kg(-1) injection, the optimal PDT response occurred with a 12 h delay and with the same irradiation parameters as described above, in this case the tumor response showing 40% growth. Considering the tumor volume doubling time, the value was 6.5 days in the control group and increased to 13.5 days with SIM01. Thus, SIM01 may be a powerful sensitizer characterized by strong in vitro and in vivo phototoxicity and faster tissue uptake and elimination than m-THPC.
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PMID:Synthesis, and in vitro and in vivo evaluation of a diphenylchlorin sensitizer for photodynamic therapy. 1269 32

In this study we investigated the feasibility of mixed liposomes formed by dimyristoyl-sn-glycero-phosphatidylcholine (DMPC) and cationic gemini surfactant (Gemini 1) loaded with the chlorin m-tetrahydroxyphenylchlorin (m-THPC), in photodynamic therapy (PDT) for glioma. To this aim, an in vitro study was carried out by employing various human glioblastoma cell lines (A172, DBTRG, LN229, U118). The following liposomal formulations were tested: (i) DMPC and Gemini 1; (ii) m-THPC in DMPC in the absence or (iii) in the presence of Gemini 1 in the molar ratio 8:2; 7:3, and 6:4. The presence of Gemini 1 significantly increased the intracellular uptake of chlorin in all cell tested although with a different extent: LN229>U118>A172>DBTRG. The cytotoxicity of chlorin-loaded liposomes was then tested by cloning efficiency performed on different cultures, before and after irradiation with laser light at 652nm, at a Fluence Rate of 200mW/s for 100s, with a total Fluence of 20J/cm(-2). In the absence of irradiation, the different liposomal formulations induced a cytotoxicity in less than 30% of glioblastoma cells. On the contrary, irradiation induced total destruction of all cultures treated with m-THPC/DMPC+Gemini 1 in the ratios 8:2, or 7:3, or 6:4.
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PMID:Cationic liposomes, loaded with m-THPC, in photodynamic therapy for malignant glioma. 1706 75

Liposomes formulated with dimyristoyl-sn-glycero-phosphatidylcholine, DMPC, and either one of the cationic gemini surfactants (S,S)-2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonio)butane bromide, 1a, and (S,R)-2,3-dimethoxy-1,4-bis(N-hexadecyl-N,N-dimethylammonio)butane bromide, 1b, were investigated as vehicles of the photosensitizer m-tetrahydroxyphenylchlorin, m-THPC, to cell models of malignant glioma. The delivery efficiency of DMPC/1a and DMPC/1b liposome formulations were evaluated on the murine glioblastoma cell line C6 and on the human glioblastoma cell line LN229 by flow cytometry and laser scanning confocal microscopy. The stereochemistry of the spacer of the gemini was found to strongly influence the delivery efficiency of m-THPC to cells, the mode of interaction with the cell membrane, and the intracellular distribution of m-THPC. The physicochemical features of liposomes were investigated with the aim of explaining the parameters that control their biological features. Differences that could account for the different biological activity of the formulations concern the values of surface potential and the environment of m-THPC at the water/liposome interface.
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PMID:Efficiency of liposomes in the delivery of a photosensitizer controlled by the stereochemistry of a gemini surfactant component. 1992 6

Photodynamic therapy (PDT) is a noninvasive and light-activated method for cancer treatment. Two of the vital parameters that govern the efficiency of PDT are the light irradiation to the photosensitizer and visual detection of the selective accumulation of the photosensitizer in malignant cells. Herein, we prepared an integrated nanoplatform for targeted PDT and imaging of cancer cells using folic acid and horseradish peroxidase (HRP)-bifunctionalized semiconducting polymer dots (FH-Pdots). In the FH-Pdots, meta-tetra(hydroxyphenyl)-chlorin (m-THPC) was used as photosensitizer to produce cytotoxic reactive oxygen species (ROS); fluorescent semiconducting polymer poly[2-methoxy-5-((2-ethylhexyl)oxy)-p-phenylenevinylene] was used as light antenna and hydrophobic matrix for incorporating m-THPC, and amphiphilic Janus dendrimer was used as a surface functionalization agent to conjugate HRP and aminated folic acid onto the surface of FH-Pdots. Results indicated that the doped m-THPC can be simultaneously excited by the on-site luminol-H2O2-HRP chemiluminescence system through two paths. One is directly through chemiluminescence resonance energy transfer (CRET), and the other is through CRET and subsequent fluorescence resonance energy transfer. In vitro PDT and specificity studies of FH-Pdots using a standard transcriptional and translational assay against MCF-7 breast cancer cells, C6 glioma cells, and NIH 3T3 fibroblast cells demonstrated that cell viability decreased with increasing concentration of FH-Pdots. At the same concentration of FH-Pdots, the decrease in cell viability was positively relevant with increasing folate receptor expression. Results from in vitro fluorescence imaging exhibited that more FH-Pdots were internalized by cancerous MCF-7 and C6 cells than by noncancerous NIH 3T3 cells. All the results demonstrate that the designed semiconducting FH-Pdots can be used as an integrated nanoplatform for targeted PDT and on-site imaging of cancer cells.
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PMID:Small molecule-initiated light-activated semiconducting polymer dots: an integrated nanoplatform for targeted photodynamic therapy and imaging of cancer cells. 2455 72