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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A retinoblastoma-like tumour has been established and characterized in terms of growth rates in vitro and in vivo, and by histopathology and chromosome analysis. Injected tumour cells grew regularly in the vitreous body with a blood supply from the retinal vessels. The tumour tissue was histopathologically similar to that of anaplastic human retinoblastomas. Almost all the cells had a triploid chromosome number and the DNA amount in tumours was stable, suggesting a stable tumour system without drift against more anaplastic degrees. Tumour cells plated in culture flasks were grown in colonies. Evaluation of the number of clonogenic cells in treated, relative to non-treated flasks reflected a quantitative treatment response. When the cells were injected into the eyes of young rats, solid tumors were formed which grew regularly until perforation of the globes. The tumours were suitable for assessment of therapeutic response in terms of local tumour control after treatment. Photodynamic therapy (PDT) of cancers, using hematoporphyrin derivatives (HPD) and visible light, is a therapeutic modality where HPD is administered 1-5 days before local light irradiation of the tumour. The combination of HPD, light energy and oxygen produces the cytotoxic agent singlet oxygen which only exists in its active state for a few milliseconds. Using this modality, it may be possible to obtain local tumour destruction in light-irradiated areas and avoid spreading of the cytotoxic agents to other organs. The effect of PDT with purified HPD (Photofrin II) and red light has been evaluated in the characterized retinoblastoma-like tumour in vivo and in vitro. The experiments demonstrated that Photofrin II and red light destroys cells in tissue culture flasks. Local control of intraocular retinoblastoma-like tumours was obtained in up to 33% of the animals following a single treatment. Adverse effects in the present model were corneal and conjunctival damage. Generally, the effect of PDT increased with larger Photofrin II doses, higher energy doses or a shorter time interval between drug administration and light irradiation. Damage to the cornea or conjunctiva limited the maximum tolerable treatment doses in the present model. The experiments suggests that PDT is a safer treatment with Photofrin II 2.5 mg/kg and a high light energy dose than with 10 mg/kg and an equivalent lower light energy dose. In tissue culture flasks, the cell inactivation did not depend on the light energy rate but only on the total delivered energy dose. The cells had a low capacity to repair sublethal damage.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effect of photodynamic therapy on a retinoblastoma-like tumour. An experimental in vitro and in vivo study on the potential use of photodynamic therapy in the treatment of retinoblastoma. 217 29

By means of laser scanning fluorescence microscopy the intratumoral localization patterns of several photosensitizers in LOX tumors in nude mice were studied. Lipophilic dyes such as P-II (Photofrin II), 3-THPP tetra(3-hydroxyphenyl)porphin, TPPS1 (tetraphenylporphine monosulfonate), TPPS2a (tetraphenylporphine disulfonates with the sulfonate groups on adjacent rings), A1PCS1 (aluminium phthalocyanine monosulfonate) and A1PCS2 (aluminium phthalocyanine disulfonates) localized mainly in tumor cells. The fluorescence intensity of these dyes increased from 4 h to 48 h post-injection and the fluorescence was still observable 120 h post-injection. The more hydrophilic dyes such as TPPS2o (tetraphenylporphine disulfonates with the sulfonates groups on opposite rings), TPPS3 (tetraphenylporphine trisulfoantes), TPPS4 (tetraphenylporphine tetrasulfonates), A1PCS3 (aluminium phthalocyanine trisulfonates) and A1PCS4 (aluminium phthalocyanine tetrasulfonates) localized mainly extracellularly in the tumorous stroma. The fluorescence intensity of these dyes decreased from 4 h to 48 h post-injection. 120 h post-injection no significant fluorescence of these dyes could be seen in the tumors. The data are discussed in relation to what is known about the in vivo photosensitizing efficiency of some of the dyes.
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PMID:Localization of potent photosensitizers in human tumor LOX by means of laser scanning microscopy. 220 72

The metabolic response of mammary carcinoma in the C3H mouse to photodynamic therapy (PDT) was measured using in vivo 31P nuclear magnetic resonance (31P-NMR) spectroscopy and pH microelectrodes. Twenty-four hours after administration of Photofrin II (12.5 mg/kg), the tumor was subjected to photoactivation using an argon dye laser. Optical treatment doses were 200, 400, and 600 J/cm2 and corresponded to the following tumor control doses: TCD10/30, TCD50/30, and TCD90/30, respectively. In vivo 31P-NMR spectra and pH micro-electrode measurements were obtained prior to treatment and at 4, 24, 48, and 72 h and 1 week post-treatment. The data revealed a significant (P less than 0.0002) alkalosis as indicated by the pH measured by NMR compared to pH measured by microelectrodes at all treatment levels and time points. Spectral differences between treatment groups were apparent as early as 4 h after treatment. The ratio of beta-nucleoside triphosphate to inorganic phosphate at 4 h after treatment was significantly (P less than 0.01) smaller for 600 J/cm2 treatment than for 200 J/cm2 treatment. At curative (600 J/cm2) levels, from 48 h on, no phosphate resonances were detected in the spectra. The pH measured by NMR transiently decreased from pretreatment levels after 200 and 400 J/cm2 treatment (P less than 0.002, P less than 0.009, respectively), while no change in pH from pretreatment values was found after 600 J/cm2 treatment. The data suggest that the early metabolic response of mammary carcinoma to PDT, as indicated by 31P-NMR spectroscopy, is dose dependent, and may be a sensitive indicator of biological outcome to treatment.
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PMID:Dose-dependent metabolic response of mammary carcinoma to photodynamic therapy. 231 47

Mono-L-aspartyl chlorin e6 (NPe6) is a photosensitizer that possesses properties such as chemical purity and a major absorption band at 664 nm which are potentially exploitable for photodynamic therapy (PDT). The current investigation examined pharmacological and photosensitizing parameters of NPe6 in tumor and normal tissues in mice. [14C]NPe6 was used to obtain quantitative tissue distributions of the photosensitizer as a function of: (a) time following administration; (b) drug dose; (c) mode of drug administration; and (d) tumor size. The in vivo photosensitizing efficiency of NPe6 was compared directly to Photofrin II in experiments which evaluated tumor responses and induction of normal skin damage. Initial PDT experiments demonstrated that NPe6 was ineffective at inducing tumor cures when a 24-h time interval (between drug administration and light treatment) was used. However, PDT-induced tumor cures were obtained when NPe6 was administered 4-6 h prior to light exposure, and these NPe6-PDT treatment parameters were as effective as standard Photofrin II-mediated PDT. Interestingly, the level of PDT-induced normal skin damage was significantly greater for Photofrin II than for NPe6 at comparable drug and light doses. An analysis of pharmacological data and PDT time interval requirements suggests that plasma concentrations of NPe6 may be a more important predictive factor than tumor tissue levels of the photosensitizer for the production of PDT-mediated tumor cures. The results of this investigation indicate that NPe6 is an effective tumor photosensitizer with in vivo clearance properties that eliminate the side effect of prolonged normal skin photosensitization.
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PMID:Tissue distribution and photosensitizing properties of mono-L-aspartyl chlorin e6 in a mouse tumor model. 235 46

Porphyrin dimers 9 with either linkages and possible isomers bis[1-[6,7-bis[2-(methoxycarbonyl)ethyl]-1,3,5,8-tetramethyl-2- vinylporphin-4-yl]ethyl] ether (10) bis[1-[6,7-bis[2-(methoxycarbonyl)ethyl]-1,3,5,8-tetramethyl-4- vinylporphin-2-yl]ethyl] ether (11), and 1-[6,7-bis[2-(methoxycarbonyl)ethyl]-1,3,5,8-tetramethyl-2-vinylporph in- 4-yl]ethyl 1-[6,7-bis[2-(methoxycarbonyl)ethyl]-1,3,5,8-tetramethyl-4-vinylporph in- 2-yl]ethyl ether (12) were synthesized from the corresponding (1-hydroxyethyl)vinyldeuteroporphyrin IX dimethyl esters (Hvd). The pure Hvd isomers 2-(1-hydroxyethyl)-4-vinyldeuteroporphyrin IX dimethyl ester (7) and 4-(1-hydroxyethyl)-2-vinyldeuteroporphyrin IX dimethyl ester (8) were obtained from 2-acetyl-4-(1-hydroxyethyl) deuteroporphyrin IX dimethyl ester (3) and 4-acetyl-2-(1-hydroxyethyl)deuteroporphyrin IX dimethyl ester (4). Porphyrins 3 and 4 were prepared either by partial reduction of 2,4-diacetyldeuteroporphyrin IX dimethyl ester (2) or by oxidation of hematoporphyrin IX dimethyl ester (1) by using tetra-n-propylammonium perruthenate (Prn4N)(RuO4) with N-methylmorpholine N-oxide as an oxidizing agent. The in vivo photosensitizing ability and therapeutic ratios of dimers 9-12 were compared with that of Photofrin II in the SMT-F tumor growing subcutaneously in DBA/2 Ha mice. These dimers were found to have better tumoricidal activity than Photofrin II with reduced skin phototoxicity.
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PMID:Porphyrin dimers as photosensitizers in photodynamic therapy. 236 83

Laser excitation of photodynamic agents localizing in colonic tumors may allow the early diagnosis and treatment of colon cancer. The efficacy of these agents requires a high ratio of tumor to background photosensitizer accumulation and fluorescence. To assess normal colonic background fluorescence and hematoporphyrin accumulation 31 rats were studied after an intravenous injection of Photofrin II (PF-II) at a dose of 5 mg/kg. An increase in mucosal fluorescence and porphyrin content was noted in the cecum 24 hours after injection. Cecal accumulation of PF-II may affect its efficacy in the localization and treatment of cecal tumors. Further investigation into the mechanism and clinical significance of this finding is needed.
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PMID:Photofrin II localization in rat cecum. 252 16

The relationship between levels of in vivo accumulated photosensitizer (Photofrin II), photodynamic cell inactivation upon in vitro or in vivo illumination, and changing tumor oxygenation was studied in the radiation-induced fibrosarcoma (RIF) mouse tumor model. In vivo porphyrin uptake by tumor cells was assessed by using 14C-labeled photosensitizer, and found to be linear with injected photosensitizer dose over a range of 10 to 100 mg/kg. Cellular photosensitivity upon exposure in vitro to 630 nm light also varied linearly with in vivo accumulated photosensitizer levels in the range of 25 to 100 mg/kg injected Photofrin II, but was reduced at 10 mg/kg. Insignificant increases in direct photodynamic cell inactivation were observed following in vivo light exposure (135 J/cm2, 630 nm) with increasing cellular porphyrin levels. These data were inconsistent with expected results based on in vitro studies. Assessment of vascular occlusion and hypoxic cell fractions following photodynamic tumor treatment showed the development of significant tumor hypoxia, particularly at 50 and 100 mg/kg of Photofrin II, following very brief light exposures (1 min, 4.5 J/cm2). The mean hyupoxic cell fractions of 25 to 30% in these tumors corresponded closely with the surviving cell fractions found after tumor treatment in vivo, indicating that these hypoxic cells had been protected from PDT damage. Inoculation of tumor cells, isolated from tumors after porphyrin exposure, into porphyrin-free hosts, followed by in vivo external light treatment, resulted in tumor control in the absence of vascular tumor bed effects at high photosensitizer doses only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen limitation of direct tumor cell kill during photodynamic treatment of a murine tumor model. 252 60

Cell survival was investigated in an intraocular retinoblastoma-like tumour 30 min to 48 h after photodynamic therapy. The survival of the cells was assessed by an in vivo to in vitro colony forming assay, estimated by either the plating efficiency of the treated tumour cells compared to non-treated cells or the number of clonogenic cells per mg excised tumour. Curves showing cell survival as a function of the time between light irradiation and excision of the intraocular tumours were biphasic. This suggests more than one PDT tissue destruction mechanism in vivo (i.e. an early direct cell damage plus a subsequent late damage occurring in the tumour tissue left in situ after treatment). The delayed mechanism may be due to changes in the environment of the tumours probably caused by vascular damage. Tumour cells sensitised by Photofrin II in vivo and excised from the eyes were damaged by light when irradiated in vitro and this was dependent on the light energy dose. This showed that cellular Photofrin II uptake in the eye tumours was sufficient for direct cell damage and thus supports the suggestion that direct and indirect tumour destruction occurs in this eye tumour after photodynamic therapy.
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PMID:Photodynamic therapy effect in an intraocular retinoblastoma-like tumour assessed by an in vivo to in vitro colony forming assay. 252 1

The destructive effect on tumour tissue and on normal eye tissue of photodynamic therapy has been investigated in rat eyes containing fast growing retinoblastoma-like tumours. Tumour response was described in terms of local control 90 days after treatment. The curability increased up to a maximum when large Photofrin II doses or light energy doses were administered. Early damage of conjunctiva or cornea also increased with large treatment doses and was an important limitation factor for improvement of the curability in the current model. The level of normal tissue damage decreased rapidly with increasing intervals between administration of Photofrin II and light, suggesting that conjunctival or corneal damage may not be a limitation factor 3-5 days after Photofrin II administration. A reciprocal relationship between light energy doses and Photofrin II doses was demonstrated both for curability and for the normal tissue damage. The results suggested that 2.5 mg/kg Photofrin II in combination with an extended light irradiation provoked less normal tissue damage than 10 mg/kg Photofrin II in combination with an equivalent shorter light exposure in order to obtain 15% curability of the animals.
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PMID:Photodynamic therapy of experimental intraocular retinoblastomas--dose-response relationships to light energy and photofrin II. 252 65

The distribution and elimination of [14C]PII, the radioisotopically-labeled equivalent of the mixture of porphyrins known as Photofrin II used in the photodynamic treatment of solid tumors, were determined in tumor-free and SMT-F tumor-bearing DBA/2 Ha-DD mice. Following i.p. injection, drug was absorbed from the peritoneum with a half-life of about 1 h; elimination from plasma was rapid, declining about 1.4 logs in concentration over 48 h following i.v. administration. However, some [14C]-activity was still detectable after 75 days. Normal tissues take up the drug within about 7.5 h after administration, with peak concentrations distributed as follows: liver, adrenal gland, urinary bladder greater than pancreas, kidney, spleen greater than stomach, bone, lung, heart greater than muscle much greater than brain. Only skeletal muscle, brain, and skin located contralaterally to subcutaneously implanted SMT-F tumors had peak [14C]-activities lower than tumor tissue; skin overlying SMT-F tumors showed concentrations not significantly different (P greater than 0.3) from tumor. After 75 days all tissues examined retained some fraction of [14C]-activity, ranging from 16% for kidney to 61% for spleen, of the initial peak tissue levels. The primary route of elimination of Photofrin II was through the bile-gut pathway, with greater than 59% of the administered [14C]-activity recovered in the feces, and only about 6% in the urine, over 192 h. HPLC analyses of fecal extracts showed that mostly monomeric and other low molecular weight porphyrin components of Photofrin II were eliminated. The higher molecular weight oligomeric fractions of Photofrin II were retained in liver and spleen up to 14 days after injection.
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PMID:Distribution and elimination of Photofrin II in mice. 252 53


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