Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Flow cytometry (FCM) was used to investigate the effect of mitomycin C (MC) on the cellular uptake of Photofrin II (PII) in a cultured human colon adenocarcinoma cell line (WiDr). The surface area of the cells increased as they passed through the cell cycle from G0/G1 to G2/M phase. MC retarded the cells in G2/M phase and enhanced the surface area of the cells. A 1.3-2.3-fold increase in the cell surface area and a 1.3-2.7-fold increase in the cellular uptake of PII in the tumor cells was observed after 2 h-8 h incubation with MC. Within each sample, an almost linear relationship between the intensity of PII fluorescence in the cells and the surface area of the cells was found. However, for the cells incubated with MC the surface area was not the only determinant of PII uptake. Effects of MC on the cell cycle, the cell surface area and the permeability of the cell membrane are suggested as possible reasons for the increase of cellular uptake of PII in the tumor cells.
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PMID:Effect of mitomycin C on the uptake of photofrin II in a human colon adenocarcinoma cell line. 153 82

Dunning R3327-AT prostate carcinomas growing in Fischer X Copenhagen rats were treated with interstitial photodynamic therapy (PDT--15 mg/kg Photofrin II 4 hours before illumination with 630-nm light via four parallelly implanted optical fibers) at different light intensities. Forty to 60 minutes after treatment, 31P-nuclear magnetic resonance spectra of tumors in anesthetized animals were obtained at 2.35 Tesla using surface coil localization. Areas under resonance peaks were normalized to the area under the peak of a phosphorus standard positioned at a fixed distance on the opposite side of the surface coil. Tumor concentrations of phosphomonoesters and phosphodiesters showed no change after tumor light doses up to 3000 J. Phosphocreatine, alpha-adenosine triphosphate (ATP), beta-ATP, and gamma-ATP signals decreased and inorganic phosphate signals increased with increasing light doses. The intratumor pH did not change significantly at these short times after PDT. In other R3327-AT and R3327-H tumor-bearing animals, [3H]misonidazole was administered 30 minutes prior to PDT treatments of both tumors. Twenty-four hours later, the tumors were resected in toto, and levels of retained [3H]misonidazole were determined in lased tumor specimens by liquid scintillation procedures. The amount of [3H]misonidazole activity in tumor tissue (covalently bound after hypoxic reduction) increased with light doses up to 3000 J. Sensitizer-adduct formation was found to correlate with the ratio of the concentration of inorganic phosphate to that of beta-ATP, both of which are presumed measures of tumor oxygenation status. These measurements have high-lighted the heterogenous nature of the oxygenation status of these experimental tumors. The precision of each assay for estimating tumor oxygenation is discussed.
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PMID:Nuclear magnetic resonance spectroscopy and sensitizer-adduct measurements of photodynamic therapy-induced ischemia in solid tumors. 174 18

Although the sequence and time interval effects of combined photodynamic therapy (PDT) and hyperthermia tumor treatments have been studied using survival curves, tumor regrowth, and cloning assays, the metabolic response to combined treatment measured by nuclear magnetic resonance (NMR) spectroscopy has not yet been clarified. In this study, mammary carcinoma in the flank of C3H mice was subjected to PDT (12.5 mg/kg Photofrin II, 632 +/- 1 nm at 200 J/cm2) and water bath hyperthermia (43.5 degrees C, 30 min) with no delay or 4 h delay between treatments. In vivo 31P-NMR spectroscopy was employed to measure energy metabolism and pH of the tumors before and serially after treatment for up to 1 week. The data revealed significant differences in the time course of high energy phosphate levels between treatment combinations, which may reflect the biological effectiveness of the combined treatments. Our observations indicate that 31P-NMR spectroscopy can be used to evaluate the metabolic response of tumors to treatment with combined PDT and hyperthermia.
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PMID:In vivo 31P NMR study of combined hyperthermia and photodynamic therapies of mammary carcinoma in the mouse. 179 55

The distribution of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AIPCS4) in tissues of BALB/c nu/nu nude mice bearing the LOX human melanoma was measured fluorimetrically at different times after intraperitoneal injection of the drugs, 20 mg/kg body weight. The plasma levels of the drugs as well as the excretion in feces and urine were also determined. The plasma concentrations of both drugs were found to build up in a similar manner during the first 30 min after injection. Thereafter, the plasma level of AIPCS4 decreased exponentially with an elimination half-life of 1.5 hr. The kinetics of elimination of P-II from the plasma were consistent with a 2-compartment model, with 90% of sensitizer lost with a half-life of about 5 hr, and the remaining fraction with a half-life of 30 hr. About 80% of the injected dose of P-II was excreted in the feces during the 7-days following injection, while 77% of AIPCS4 was excreted in the urine during the same period. After injection of a dose of 20 mg/kg, the concentrations of P-II in the LOX tumor as well as in the skin, muscle, brain, heart, lung, kidney and liver increased for about 24 hr, then remained constant or decreased slowly for the next 48 hr, after which they decreased slightly faster. On the other hand, the concentrations of APICS4 in most tissues as well as in the tumor peaked at about 30 min, then decreased with a half-life of between 1.5 and 3 hr. The tumor/skin concentration ratio was about 1 for both drugs (1-24 hr after injection). The tumor/muscle concentration ratio was about 2 for P-II at all sampling times, and maximally 10 (at 18 hr after injection) for AIPCS4. In the present tumor model, the tumor/tissue concentration ratio for all tissues at 1 hr and at 24 hr after the injection was equal for the 2 drugs or higher for AIPCS4.
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PMID:Sensitizer for photodynamic therapy of cancer: a comparison of the tissue distribution of Photofrin II and aluminum phthalocyanine tetrasulfonate in nude mice bearing a human malignant tumor. 182 1

Asynchronous populations of mouse EMT-6 tumor cells were treated with Photofrin II and exposed to various doses of 630 nm light in slowly stirred suspensions which had been equilibrated with various concentrations of oxygen. Survival curves were generated with cells exposed to 20 micrograms/ml Photofrin II in tissue culture medium for 1 h, a procedure which made it possible to remove more than 50% of the drug by washing. It is expected that under these conditions the drug would be loosely bound to cell surface and plasma membranes and in the cellular cytosol. Survival curves were also generated with cells exposed to 5 micrograms/ml Photofrin II for 20-24 h, a procedure which resulted in greater than 90% of the drug being tightly bound within cells, presumably to cellular lipids and membranes. Oxygen was obligatory for killing cells which had been exposed for both "short term" and "long term" to Photofrin II. After 30-40 min of pregassing cells with nitrogen gas which contained precise levels of oxygen, the concentration required to reduce rates of cell killing to 50% of maximum was approximately 0.5% O2 (gas phase) for short-term drug exposures and less than or equal to 0.05% O2 for long-term drug exposures. Even after pregassing times of 90-120 min prior to light administration, a Km of approximately equal to 0.1% O2 was observed for cells exposed to the drug for the longer time. When the same cells were exposed to 137Cs gamma rays in this irradiation chamber, no change in radiation sensitivity was observed after 30 min of pregassing cells with all oxygen concentrations studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen dependency of tumor cell killing in vitro by light-activated Photofrin II. 182 59

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 TPPS1 (tetraphenylporphine monosulfonate), TPPS2a (tetraphenylporphine disulfonates with the sulfonate groups on adjacent rings), AlPCS1 (aluminium phthalocyanine monosulfonate) and AlPCS2 (aluminium phthalocyanine disulfonates) localized mainly in tumor cells. The fluorescence intensity of these dyes increased from 4 h to 48 h postinjection and the fluorescence was still observable 120 h postinjection. The more hydrophilic dyes such as TPPS3 (tetraphenylporphine trisulfonates), TPPS4 (tetraphenylporphine tetrasulfonates), and AlPCS4 (aluminium phthalocyanine tetrasulfonates) localized mainly extracellularly in the tumorous stroma. The fluorescence intensity of these dyes decreased from 4 h to 48 h postinjection. 120 h postinjection no significant fluorescence of these dyes could be seen in the tumors. P-II (Photofrin II), 3-THPP [tetra(3-hydroxyphenyl)porphine], TPPS2o (tetraphenylporphine disulfonates with the sulfonate groups on opposite rings) and AlPCS3 (aluminum phthalocyanine trisulfonates) had a combined localization pattern, i.e. a strongly cytoplasmic membrane-localizing pattern and a weakly intracellular distribution pattern, although some fluorescence could be seen in the tumorous stroma. 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. 182 11

Athymic BALB/c nude mice, bearing a human melanoma LOX, were given the photosensitizing drug Photofrin II (10 mg/kg body wt.) intraperitoneally. The mice were also given one of the following chemicals intraperitoneally: glucose, galactose and glucose plus nordihydroguaiaretic acid (NDGA) which is an inhibitor of glycolysis. Multiple injections of glucose (3 g/kg body wt. given at -1, 0, +1 and +3 h relative to the injection of 10 mg/kg of Photofrin II at time 0) resulted in a significant increase in the uptake of Photofrin II in the tumor 4 h after a Photofrin II injection, while the uptake of Photofrin II in the other tissues remained unchanged. Administration of galactose had no significant effect on the uptake of Photofrin II in the tissues studied (tumor, muscle, skin and liver). NDGA seemed to abolish the effect of glucose injection.
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PMID:The effect of glucose administration on the uptake of photofrin II in a human tumor xenograft. 182 12

The patterns of in vitro intracellular and in vivo intratumoral localization of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AlPCS4) in human melanoma LOX were studied by means of computer-enhanced video fluorescence microscopy (CEVFM). The hydrophobic drug P-II localized diffusely in the perinuclear fraction of the cytoplasm of the LOX cells cultivated in vitro. Light exposure did not result in any observable change in the localization pattern. The hydrophilic dye AlPCS4 was distributed as granular and grain patterns in the cytoplasm before light exposure, in exactly the same pattern as that of acridine orange incubated in the same cells, which is known to emit red fluorescence from lysosomes, thus indicating that AlPCS4 was also primarily localized in the lysosomes of the LOX cells. After light exposure the distribution of the intracellular AlPCS4 fluorescence was altered and the intensity increased. In vivo, P-II had a combined cellular localization pattern (i.e. a strongly cytoplasmic membrane-localizing pattern and a weakly intracellular distribution pattern) and an extracellular distribution pattern in the tumor tissue, while the AlPCS4 fluorescence was seen mainly in the stroma of the tumor. The total fluorescence intensity of P-II and AlPCS4 in the LOX tumor tissue at different times after injection was quantitatively determined by means of CEVFM.
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PMID:Location of P-II and AlPCS4 in human tumor LOX in vitro and in vivo by means of computer-enhanced video fluorescence microscopy. 182 13

The tumoricidal response of subcutaneously growing SMT-F adenocarcinoma implanted into syngeneic DBA/2 mice to Photofrin II-sensitized photodynamic therapy (PDT) was statistically significantly enhanced by the addition of a single dose of intravenously administered recombinant human tumor necrosis factor-alpha (rHuTNF-alpha). The interaction appeared to be approximately additive, i.e. tumor response to PDT plus rHuTNF-alpha was about the same as that observed by doubling the PDT dose. Conversely, rHuTNF-alpha did not significantly potentiate the cutaneous phototoxicity in mouse feet due to PDT. These data suggest that combination therapy should be considered for improving tumor response while retaining treatment selectivity in human malignancies.
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PMID:Potentiation of photodynamic therapy in mice with recombinant human tumor necrosis factor-alpha. 182 33

Photodynamic therapy (PDT) is a potential treatment for peritoneal carcinomatosis. However, little data is available regarding the relative distribution of sensitizer to tumor and intra-abdominal organs, optimal route of sensitizer administration, and maximal tolerated light dose. Tumor and normal tissue sensitizer levels were measured by tissue extraction 3, 24, 48 and 72 h after 10 mg/kg of Photofrin II was given intraperitoneally (IP) or intravenously (IV) in a mouse peritoneal tumor model, and the maximal tolerated PDT light dose determined. Equivalent tumor sensitizer levels were obtained regardless of the route of sensitizer administration. Route of administration, however, did affect the kinetics of tumor sensitizer elimination, with the half-time for elimination (T1/2) 113.6 h for IP drug and 60.6 h for IV drug. Route of administration also affected sensitizer levels in several intra-abdominal organs, resulting in somewhat higher tumor to liver and kidney levels at 24 and 72 h after IP sensitizer administration. Despite these tissue distribution differences, route of sensitizer administration did not significantly affect PDT toxicity or mortality when mice were treated with 630 nm light. The maximum tolerated light dose was 1.04 J/cm2. These parameters will prove helpful in designing large scale animal trials assessing the efficacy and safety of intra-abdominal PDT.
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PMID:Intravenous vs intraperitoneal sensitizer: implications for intraperitoneal photodynamic therapy. 182 31


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