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)

Fluorescence imaging using hematoporphyrin derivative (HpD) or Photofrin II as a tumor marker has been used for localization of early bronchogenic carcinoma. Wider clinical application of HpD or Photofrin II as a cancer imaging agent has been hampered by the potentially serious and prolonged skin photosensitivity. Using a sensitive fluorescence bronchoscope system with a ratio fluorometer probe, carcinoma in situ was detected in four patients with low dose Photofrin II (0.25 mg/kg) with no apparent skin phototoxicity to 30 J/cm2 visible light on skin photosensitivity test.
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PMID:Detection of early lung cancer using low dose Photofrin II. 213 75

Endoscopic detection of small tumors is key to the early diagnosis and treatment of malignancy. This paper describes a simple, endoscopic detection system which enables tumor localization and a permanent record based on the laser-induced fluorescence of dihematoporphyrin ether (LIFD). Spectral analysis of dihematoporphyrin ether (DHE, Photofrin II) was performed with a Perkin Elmer LS-5 scanning fluorimeter. DHE at concentrations of 50 micrograms/ml and 5 micrograms/ml in 95% ethanol were tested, demonstrating fluorescence quenching at 50 micrograms/ml DHE at 406 nm excitation. This phenomenon was not observed at 442 nm excitation. Based on this data and the availability of the helium cadmium laser, a series of endoscopic detection systems was developed and tested utilizing a LiConix 4240NB helium cadmium laser (TEMoo, 442 nm, 40 mW). A fiber with a microdiverging (MDL) lens was used. Irradiance achieved at the tip of the fiber was 31.58 mW/cm2 for MDL. A Corning 34832 (550 nm) sharp cutoff barrier filter was coupled to an Olympus OES BF2T10 bronchoscope. Successful detection of LIFD was obtained. Direct observation of LIFD is possible when wearing Laserguard argon safety goggles (OD 15 at 488 nm, OD 11 at 514 nm). Photographic recording of LIFD was performed with the following cameras and parameters: Olympus OM-2S camera (OM2) with EES135 film (ISO 1600) with a 4-second exposure (method 1) and the Olympus OES SCP-10 instant camera with Polaroid 779 (ISO 640) film and a 120-second exposure (method 2). The photographic methods demonstrate the red fluorescence of DHE on filter paper disks at concentrations of 0.5 micrograms/ml (500 ng/ml). (ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Methods for the endoscopic photographic and visual detection of helium cadmium laser-induced fluorescence of Photofrin II. 213 96

Thromboxane and prostacyclin levels in serum were measured following photodynamic therapy (PDT) to assess the role of these vasoactive agents on vascular damage and tumor destruction. Sprague Dawley rats were given injections i.v. of Photofrin II doses ranging from 0 to 25 mg/kg. Twenty-four h later, the right hindlimbs of animals bearing chondrosarcoma tumor or controls were exposed to 0-135 J/cm2 630 nm light. Serum concentrations of thromboxane and prostacyclin were determined by radioimmunoassay. A dose-response relationship was established between the amount of photosensitizer administered and the light dose delivered with the release of thromboxane immediately following PDT. Treatment of tumor induced higher levels of thromboxane than did the treatment of tumor-free tissue, suggesting that tumor is more sensitive to PDT-induced damage. The porphyrin and light doses found to induce the release of thromboxane into serum were the same as those required to evoke vascular stasis and tumor destruction. Prostacyclin release was not altered by PDT. The administration of indomethacin (10 mg/kg, i.p.) 3 h before light treatment was found to suppress the intravascular release of thromboxane at the highest porphyrin and light doses studied. Indomethacin treatment also inhibited PDT-induced vascular stasis and tumor destruction, suggesting that the release of thromboxane is linked to these events. Since prostacyclin levels in serum were unchanged following PDT treatment of tumor and controls, thromboxane release appears to be a specific response to PDT and may mediate the vascular stasis observed following PDT.
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PMID:Role of thromboxane and prostacyclin release on photodynamic therapy-induced tumor destruction. 213 57

Several studies have examined the synergism of hyperthermia or chemotherapy agents in combination with photodynamic therapy (PDT) to enhance tumor eradication. In our unique approach to treatment, multiple photosensitizers and wavelengths were used: two photosensitizers, Photofrin II and meso-tetra-(4-sulfonatophenyl)-porphine (TPPS4), irradiated at the appropriate therapeutic wavelength for each photosensitizer. EMT-6 mammary tumors were induced in the flanks of BALB/c mice. The mice were assigned to a control group (50 mice) or treatment group (150 mice). All treatment animals and some control animals received photosensitizing drug (5 mg/kg of TPPS4, 5 mg/kg of Photofrin II, or 2.5 mg/kg of both TPPS4 and Photofrin II). All treatment animals and some control animals also received light treatment (630 nm for TPPS4 and/or 658 nm for Photofrin II). The results show that the approach using both drugs and the corresponding therapeutic wavelengths enhanced the effectiveness of PDT. This approach achieved a cure rate of up to 100%, which was, depending on the light intensity used, as much as 40% greater than the rate achieved by the approach using one drug and one wavelength. The results also show that lesser amounts of drug and/or light may be required if both drugs and wavelengths are used, thus lowering the chances of side effects common to PDT. Furthermore, the results indicate that the increased tumor kill is due to a synergistic effect of the two photosensitizers that was tested on the tumor microvasculature in the first few hours after PDT.
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PMID:Use of multiple photosensitizers and wavelengths during photodynamic therapy: a new approach to enhance tumor eradication. 213 4

The cellular uptake of Photofrin II (PII) was studied using fluorescence imaging and chemical extraction. The influence of serum and low density lipoproteins (LDL) was examined under a variety of experimental conditions employing cultured human cells of different origins as well as a subcutaneously SMT-F tumor implanted in mice. Results showed that serum inhibited PII uptake. In general, LDL also inhibits PII uptake with the exception of an initial increase in the first 10-30 min when the cellular concentration of PII was measured by fluorescence imaging instead of chemical extraction. Our results suggest a possible de-aggregation process occurring upon internalization or binding of PII to LDL.
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PMID:The effects of low density lipoproteins on uptake of Photofrin II. 213 30

A comparative kinetic observation of the in vivo biolocalization of Photofrin II (P-II) and aluminum phthalocyanine tetrasulfonate (AIPCS4) in a transplanted human malignant tumor LOX and in normal tissues of nude mice has been made by means of highly light-sensitive video intensification microscopy at various intervals after i.p. administration. In the human tumor LOX, transplanted to athymic nude mice, fluorescence of P-II was observed on the membrane and in the cytoplasm of tumor cells, and in the stroma 4-48 hr post-injection. From 72 hr post-injection almost all fluorescing P-II had disappeared from the membrane of the tumor cells while strong fluorescence was still found in the stroma. AIPCS4 fluorescence was seen mainly in tumorous stroma with none detected in the tumor cells. Almost no fluorescence was found in the tumorous stroma 24 hr after injection. In most normal tissues observed, P-II was eliminated at a much slower rate than AIPCS4, but the in vivo biolocalization of the 2 drugs was similar. They were observed primarily where collagenous proteins are normally found, i.e. basal lamina, collagenous connective tissue, and in keratinized epithelium, renal epithelium, mononuclear phagocyte system and on the membrane of muscular cells. In addition, AIPCS4 had a strong affinity for the bronchiogenic epithelium. In the skin, P-II was distributed in keratinized epithelium, hair, hair follicles and their accessory, collagenous connective tissue of dermis, whereas AIPCS4 was present only in hair and collagenous connective tissue of dermis. No fluorescence of P-II or of AIPCS4 was found in the skin epidermis, nor in the transitional epithelium of the bladder mucosa.
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PMID:Localization of fluorescent Photofrin II and aluminum phthalocyanine tetrasulfonate in transplanted human malignant tumor LOX and normal tissues of nude mice using highly light-sensitive video intensification microscopy. 213 67

Photodynamic therapy (PDT) utilizes a photoactivatable preparation, Photofrin II, which selectively localizes in cancerous tissue and produces substances toxic to that tissue when activated by light. Whether PDT would be able to selectively destroy human malignant mesothelioma was investigated by using a human-derived malignant mesothelioma tumor subcutaneously implanted in nude mice. Human malignant mesothelioma was grown subcutaneously to a size of 0.2-0.4 cm3. Selective retention of Photofrin II was studied by measuring light-induced inhibition of cytochrome c oxidase activity in tumor, heart, and lung. Photofrin II was retained in greater quantities in tumor than in heart or lung at 24 hr after injection. Using laser light at 630 nm under varying conditions, tumor growth was measured every 2 days following PDT for 18 days. All PDT regimens were successful in destroying malignant mesothelioma. Photofrin II at 5 mg/kg was superior to 2 mg/kg (P less than 0.005), light delivered at 50 mW/cm2 x 2 hr was superior to that delivered at 200 mW/cm2 x 30 min (P less than 0.05), and a total fluence of 180 J/cm2 was equivalent to 360 J/cm2 in affecting tumor growth. Ten of 12 mice treated at 50 mW/cm2 became tumor-free and remained so for 30 days following treatment. We concluded that PDT was effective against human malignant mesothelioma in a nude mouse model without adversely affecting the animal. A role for PDT in treating patients with malignant mesothelioma may exist.
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PMID:Photodynamic therapy for human malignant mesothelioma in the nude mouse. 214 73

Among the sequence of events which occur during photodynamic therapy (PDT) are depletion of oxygen and disruption of tumor blood flow. In order to more clearly understand these phenomena we have utilized transcutaneous oxygen electrodes to monitor tissue oxygen disappearance. These results provide, for the first time, non-invasive real-time information regarding the influence of light dose on tissue oxygenation during irradiation. Measurements were conducted on transplanted VX-2 skin carcinomas grown in the ears of New Zealand white rabbits. Rabbits were treated with Photofrin II and tumors were irradiated with up to 200 kJ/m2 (500 W/m2) of 630-nm light. Substantial reductions in tumor oxygen tension were observed upon administration of as little as 20 kJ/m2. For a series of brief irradiations, oxygen tension was modulated by the appearance of laser light. Tissue oxygen reversibility appeared to be dependent upon PDT dose. Long-term, irreversible tissue hypoxia was recorded in tumors for large (200 kJ/m2) fluences. These results suggest that transcutaneous oxygen tension may be useful as a general indicator of the effectiveness of PDT and as an in situ predictor of the energy required to elicit tumor damage.
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PMID:In vivo tumor oxygen tension measurements for the evaluation of the efficiency of photodynamic therapy. 214 95

Growth and dose-response curves were established for a subcutaneously implanted isogenic fibrosarcoma in BD9 rats after treatment with photochemotherapy (PCT), using Photofrin II or polyhaematoporphyrin with superficial or interstitial 630 nm light, cyclophosphamide or gamma-irradiation. Tumour response to PCT increased with dose up to 200 J.cm-2 for superficial light or 200 J for interstitial light but no further response occurred after higher light doses. The maximum response after interstitial treatment was significantly greater than after superficial treatment where only a small margin of normal tissue was treated. The incidence of necrosis in the overlying skin was significantly less after interstitial than superficial light suggesting a better therapeutic ratio after interstitial than superficial PCT. Tumour response increased with the diameter of the treatment field after superficial light supporting the possibility of a tumour bed effect associated with PCT. The largest tumour that could be effectively treated with a single optical fibre was 12 mm. The dose-response curves for interstitial PCT and cyclophosphamide were similar but ionizing irradiation produced increasing tumour response throughout the range of doses used (5 to 30 Gy) and the maximum response was greater after radiotherapy than after PCT or chemotherapy suggesting that in this tumour model interstitial PCT is as effective as cyclophosphamide but less effective than radiotherapy.
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PMID:The response of a rodent fibrosarcoma to superficial/interstitial photochemotherapy, chemotherapy or radiotherapy. 214 11

Photofrin II (dihaematoporphyrin ether/ester, DHE) was labelled with indium-111 and its biodistribution in tumour bearing mice compared with that of 111In chloride. The uptake and clearance of 111In labelled DHE differed markedly from that of indium-111 chloride in that the former was not taken up by the tissues as much as the latter. Scintillation scanning with a gamma-camera showed marked uptake of both 111In agents at the site of the tumour, but a much lower tissue background (excluding the abdominal organs) for the mice given 111In DHE. Tumour:muscle ratios of dissected tissues were 2-3 times higher in 111In DHE treated animals as compared to the uptake of 111In chloride. There was a distinct difference in the pattern of distribution of the two 111In preparations in the tissues. The major accumulation of 111In chloride was in the kidneys, whereas the highest uptake of 111In DHE was in the liver, the organ in which unlabelled porphyrins accumulate. Extraction and testing of materials from tumours of 111In DHE treated animals indicated that most of the tumour extractable 111In had remained associated with the porphyrin in vivo up to 4 days after injection.
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PMID:Tumour scanning with indium-111 dihaematoporphyrin ether. 214 58


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