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)

Photodynamic treatment in vitro, using the photosensitizer Photofrin II and light at 630 nm, was found to liberate large amounts of prostaglandin E2 (PGE2) from mouse radiation-induced fibrosarcoma tumor cells and peritoneal macrophages, but not from L929 fibroblasts. PGE2 release was dose dependent and directly related to cell membrane disruption. It occurred rapidly and was complete within 30 min of treatment. PGE2 release could be inhibited by indomethacin, meclofenamate and extended prior exposure to dexamethasone, indicating that it was due to new production involving both the phospholipase and cyclooxygenase enzyme systems. Removal of calcium ions, necessary for phospholipase activation, from the medium did not inhibit the photodynamically induced elevated PGE2 production, possibly because of Ca2+ resupply from leaking intracellular pools.
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PMID:Release of prostaglandin E2 from cells by photodynamic treatment in vitro. 253 Oct 34

The effects of photodynamic therapy using 632 nm photoradiation emitted from an ion pumped dye laser system on the phosphate metabolite levels of rat mammary tumors were monitored by 31P-NMR spectroscopy. A dramatic decline to almost undetectable levels, in the ratio of whole tumor beta-ATP (NTP) to Pi was observed after systemic administration of 5 mg/kg Photofrin II 24 h prior to exposure of R3230AC rat mammary tumor to laser irradiation at 180 and 360 J/cm2 total fluence. This decline in ATP was accompanied by a concomitant increase in the levels of Pi relative to the total observable phosphate signals. Whole tumor pH was calculated from the chemical shift in inorganic phosphate using the water proton signal as reference. Under the same treatment conditions used to monitor the phosphate metabolites following Photodynamic Therapy, the pH of the tumor as a whole decreased approximately 0.35 units at the time when the beta-ATP to Pi ratios were lowest. This maximal decrease in whole tumor ATP levels and pH, which occurred at 4-6 h post irradiation, was followed by a gradual return to pre-treatment levels over a 24 h period. These results demonstrate that Photodynamic Therapy employing porphyrin photosensitization and monochromatic laser irradiation is effective in reducing both tumor high energy phosphate levels and pH. Depending on sensitizer dose and light fluence, metabolic inhibition, represented by depleted nucleoside triphosphates and elevated Pi, may be reversible.
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PMID:Effects of laser photodynamic therapy on tumor phosphate levels and pH assessed by 31P-NMR spectroscopy. 253 22

Four thiol-containing compounds, WR-2721, WR-149024, WR-168643 and WR-361, were compared as photoprotectors of murine feet. The protector doses were the maximal tolerated intraperitoneal doses, administered 24 h after injection of Photofrin II and 15 min before illumination with 630-nm laser light. While all four compounds were effective, only WR-2721 demonstrated a statistically significant attenuation of phototoxicity. WR-2721 was found to protect SMT-F tumors in the same mouse strain, using tumor growth delay and short-term control as endpoints. A comparison of the dose modification factors for foot and tumor responses indicated no therapeutic advantage in using WR-2721 during photodynamic treatment of these two tissues.
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PMID:Protection of murine foot tissue and transplantable tumor against Photofrin-II-mediated photodynamic sensitization with WR-2721. 255 9

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.
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PMID:Preparation and photosensitizing properties of hematoporphyrin ethers. 258 45

A Chemiluminescent System (CLS), using a Peroxyoxalate chemiluminescent solution (PCs), together with Hematoporphyrin derivative (HpD) Photofrin II., were utilized in the treatment of transplanted mammary adenocarcinomas in C3H/HeJ female mice. Tumor bearing animals aged 2-4 months were divided into five groups; Group I was the control. Groups 2 and 4 compared the effectiveness of both reagents HpD and PCs which were administered by intratumor injections fractionated over a 96 hour period. Groups 3 and 5 compared the effectiveness of PCs alone. Tests of the PCs were conducted with and without the presence of luminescence. Fifty-three percent of the animals in Group 4 and 47% of the animals in Group 2 remained tumor free 120 days after the completion of treatment. Thirty percent of the animals in Groups 2 and 4 survived one year without tumor recurrence. The results of this study suggest that a chemical light system can be a viable alternative in Photodynamic Therapy (PDT) to laser light for the activation of HpD and treatment of cancer.
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PMID:Chemiluminescence and hematoporphyrin derivative: a novel therapy for mammary adenocarcinomas in mice. 266 91

Photodynamic therapy (PDT) is the treatment of malignant lesions with visible light following the systemic administration of a tumor-localizing photosensitizer. Pharmacological and photochemical properties of the photosensitizer are combined with precise delivery of laser-generated light to produce a treatment which can offer selective tumoricidal action. Hematoporphyrin derivative (HD) and a purified component called Photofrin II are currently being used in clinical PDT. Initial patient results have been encouraging, and considerable interest has developed in the synthesis and evaluation of new photosensitizers with improved photochemical and pharmacological characteristics. In addition, there has been a gradual increase in knowledge related to in vitro and in vivo mechanisms of action of PDT. This report provides an overview of the properties and applications of PDT. Information and data related to drug development, photochemistry, subcellular targets, in vivo responses, and clinical trials of PDT are presented.
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PMID:Properties and applications of photodynamic therapy. 267 24

This paper outlines our present knowledge of photosensitizer tissue distribution, derived from preclinical animal studies, and relates it to the observed biological response to photodynamic therapy (PDT). Emphasis is placed on porphyrins (haematoporphyrin derivative (HpD), Photofrin II) and phthalocyanines (aluminum phthalocyanine sulphonate AlPcS). In mice, both groups of sensitizers show multiphasic plasma clearance kinetics with an initial rapid decline followed by further slow reduction. Residual amounts of Photofrin II are detectable 75 days after injection. Drug elimination occurs through urine and faeces, but faecal elimination predominates for Photofrin II. Circulating sensitizer greatly influences the mouse ear-swelling response, but not the foot response. Tumours and normal skin can be destroyed by vascular damage, if illumination occurs at times of maximal plasma sensitizer concentration, with no detectable sensitizer accumulation in tumour cells. Organ retention for both photosensitizer groups is similar and persistent. Organs rich in reticuloendothelial elements (liver, kidney, spleen) accumulate and retain the highest levels, skin and muscle the lowest, while normal brain tissue excludes sensitizer. The adrenal and pancreatic glands, as well as urinary bladder, also retain high amounts of Photofrin II. Tumour/skin ratios of 1 to 3:1 and 2 to 7:1 have been reported for porphyrins and sulphonated phthalocyanines respectively. Tissue destruction upon light exposure is not always correlated with photosensitizer levels, as is exemplified by liver and pancreas. Stromal sensitizer localization usually predominates in tumour and normal tissue, and often determines tumour response. Certain compounds, such as monosulphonated tetraphenylporphyrin and AlPcS, may favour parenchymal localization. The formed blood elements remain free of photosensitizer, while mast cells and macrophages accumulate especially large amounts and, upon illumination, release an array of vasoactive inflammatory and immune mediators.
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PMID:Tissue localization of photosensitizers and the mechanism of photodynamic tissue destruction. 269 28

The relation between the lifetimes of the triplet states of various porphyrins and their photosensitizing effects on the photodynamic therapy (PDT) of tumor has been examined. Diethylene-triamine pentaacetic acid ester of 4-[1-(2-hydroxy-ethyloxy)ethyl]-2-vinyl deuteroporphyrin-IX gallium (III) complex (Ga-DP), zinc (II) complex (Zn-DP), and manganese (III) complex (Mn-DP) and Photofrin II (PII) are used as the photosensitizer. The triplet lifetimes have been measured for the samples adsorbed on filter paper (FP) and found to be 57 ms (Ga-DP), 26 ms (Zn-DP), less than or equal to 10 microseconds (Mn-DP) and 9 ms (PII). The phosphorescence of Ga-DP in tumor-bearing golden hamsters are measured both in tumor tissue and in liver. They show bi-exponential decay with the lifetimes of about 5 and 20 ms. From the values, the generation rate, kct[3O2], of singlet molecular oxygen in living animal tissue may be estimated to be an order of 10(2) s-1. The PDT effects have been quantitatively investigated for in vitro experiments; upon irradiation the growth inhibitions of mouse p388 leukemia cells are obtained as a function of concentration of Ga-DP, Zn-DP, Mn-DP and PII. The experimental results indicate that the PDT effects depend essentially on the triplet lifetimes of the photosensitizers.
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PMID:Critical importance of the triplet lifetime of photosensitizer in photodynamic therapy of tumor. 278 Aug 23

The synthetic "picket fence" porphyrin, tetra(o-acetamidophenyl)porphine (TAc), as a biological photosensitizer has been evaluated both in vitro and in vivo in mitochondria from the R3230AC mammary tumor. Studies in vitro, consisting of incubation of mitochondria with TAc at a concentration of 4.0 micrograms/ml followed by photolysis, result in the inhibition of cytochrome c oxidase, proton translocating ATPase, succinate dehydrogenase, and malate dehydrogenase. The diminution in activity of the first three enzymes is approximately 2-fold greater than that seen with Photofrin II under the same conditions. Although TAc exists as four isolable atropisomers, no differences among these different forms were observed in their photosensitized inhibition of mitochondrial enzymes. Administration to tumor-bearing rats of TAc i.p. at a dose of 25 mg/kg did result in accumulation of porphyrin within the mitochondria of the R3230AC tumor as determined by subsequent irradiation of isolated mitochondria. The potential utility of TAc and related porphyrins in cancer phototherapy is discussed.
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PMID:Picket-fence porphyrins as potential phototherapeutic agents. 283 16

The sensitivity to photodynamic treatment of three plasma membrane enzymes in R3230AC mammary adenocarcinomas was assessed. The activities of Na+K+-ATPase, Mg2+-ATPase and 5'-nucleotidase in isolated membranes were measured after exposure of membranes to either hematoporphyrin derivative or Photofrin II plus light in vitro or in tumor membranes prepared from animals previously injected with 25 mg/kg Photofrin II and sacrificed at various times prior to exposure to light (in vivo-in vitro protocol). The activities of both Na+K+-ATPase and Mg2+-ATPase were inhibited at equivalent rates by Photofrin II in vitro; inhibition was drug dose and light dose related. For 5'-nucleotidase in vitro, a 10-fold higher porphyrin concentration was required to achieve a similar rate of enzyme inhibition as that for the ion-activated ATPases. Injection of Photofrin II in vivo followed by preparation of tumor plasma membranes, which were subsequently exposed to light in vitro, produced no photosensitization of 5'-nucleotidase activity at any time studied (up to 72 h after Photofrin II administration). Under the same conditions Na+K+-ATPase activity was reduced by 40-60% from 2 to 72 h after drug injection, whereas Mg2+-ATPase activity was inhibited by 10-25% over the same time course. The differential sensitivity of these three enzymes observed in this in vivo-in vitro protocol suggests that each enzyme may possess different characteristics, such as three-dimensional configuration or membrane location, that afford varying susceptibility to porphyrin photosensitization. The data also suggest that photosensitivity-induced damage to these ion-activated plasma membrane ATPases could have deleterious effects on tumor cell survival.
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PMID:Photosensitizing effects of hematoporphyrin derivative and photofrin II on the plasma membrane enzymes 5'-nucleotidase, Na+K+-ATPase, and Mg2+-ATPase in R3230AC mammary adenocarcinomas. 283 53


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