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

Photodynamic therapy (PDT) is a new experimental cancer therapy in which a photosensitizing chemical that selectively localizes within tumors is given to a tumor-bearing individual and the tumor is then irradiated by wavelengths within the visible spectrum of the photosensitizer. The only photosensitizer currently approved for human clinical trials is Photofrin-II (Pf-II). In most preclinical studies, the effectiveness of Pf-II has been assessed in implanted tumor models rather than in systems in which tumors are grown in their own connective tissue matrix. In this study, the pharmacokinetics, tumor ablation capability and cutaneous photosensitizing capacity of Pf-II were assessed in mice bearing chemically induced or ultraviolet B radiation (UVB)-induced benign skin neoplasms. Intraperitoneal administration of Pf-II (5 mg/kg body weight) to tumor-bearing animals showed maximum tumor: normal skin ratio of the photosensitizer at 72 h. When SENCAR mice bearing chemically induced tumors were irradiated with visible light corresponding to the absorption spectrum of the photosensitizer, up to 89% ablation in tumor volume at 20 d post-irradiation was observed. Animals treated with Pf-II and exposed to visible light showed significant cutaneous photosensitization for at least 6 d after-irradiation. Treatment of SKH-1 hairless mice bearing UVB-induced cutaneous neoplasms with Pf-II exhibited similar pharmacokinetics, skin tumor ablation effects and cutaneous photosensitivity. Our data indicate that Pf-II has significant activity towards the ablation of murine skin benign tumors grown in their own tissue matrix, suggesting that such a murine skin tumor model system could be valuable in evaluating the photodynamic effects of newly developed photosensitizers.
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PMID:Photodynamic therapy of murine skin tumors using Photofrin-II. 183 55

A pulsed KTP pumped dye laser (25 kHz repetition rate and 470 nsec pulse width) has been compared to a continuous wave argon ion pumped dye laser as the source of 630 nm light during in-vitro and in-vivo Photofrin-II mediated photosensitization studies. Individual experiments documented the effectiveness of each laser system on a) photosensitizer induced cytotoxicity and induction of stress protein synthesis using Chinese hamster fibroblasts; b) photobleaching of Photofrin-II in aqueous solution; c) Photofrin II mediated photosensitization of normal mouse skin; d) Photofrin II mediated photodynamic therapy of a mouse mammary carcinoma; and e) tumor temperature levels generated during laser exposure. Comparable results were obtained for both laser systems in all experiments.
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PMID:Direct comparison of in-vitro and in-vivo Photofrin-II mediated photosensitization using a pulsed KTP pumped dye laser and a continuous wave argon ion pumped dye laser. 184 75

PDT is a technique in which visible light is used in combination with photosensitizing agents to achieve a tumoricidal effect. Hematoporphyrins are the most commonly used photosensitizers in clinical practice. DHE is the active fraction of hematoporphyrin. Intravenously injected DHE is found in highest concentration in the liver followed by the spleen, kidney, tumor, skin, muscle, brain, and lungs. The strongest absorption bands for DHE are in the blue region of the spectrum, and this helps to account for the skin toxicity associated with PDT. Red light, at the wavelength of 630 nm, is usually used clinically because of its greater tissue penetration. Techniques such as photobleaching and use of photosensitizers that have weak absorption bands at the lower wavelengths may reduce cutaneous toxicity in the future. Other approaches, such as the use of monoclonal antibody-linked photosensitizers or cationic photosensitizers that are specifically localized in tumor cells, may also increase the effectiveness of PDT while decreasing toxicity. Light for PDT is usually provided by argon-pumped dye lasers or metal vapor lasers. Diode lasers will be used in the future. The use of fiber-optics and diffusing lenses allows the endoscopic and interstitial use of PDT. The mechanism of action of PDT involves the formation of singlet oxygen, which oxidizes biologic molecules and causes irreversible subcellular damage. The major in vivo effect of PDT is caused by its destruction of tumor vasculature, causing anoxia and necrosis. The use of PDT in gynecology has been limited. Several investigators have reported mixed results in treating lower genital tract intraepithelial and recurrent malignant tumors using a variety of approaches involving PDT. The use of PDT in other similar, though nongynecologic, tumors offers a direction for future research.
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PMID:Photodynamic therapy in gynecology. 195 68

Human choriocarcinoma (JEG-3) cells were transplanted into the cheek pouch of hamsters and treated with photodynamic therapy. Twenty-four hours after intraperitoneal injection of the photosensitizer dihematoporphyrin ether (DHE), 20 tumors were illuminated with 100 J/cm2 of 630-nm light from an argon pumped dye laser. Contralateral tumors served as controls. Dihematoporphyrin ether alone had no effect on tumor growth, while laser light in the absence of DHE resulted in complete regression in 3 tumors (17%), and partial regression in 4 of 18 tumors (22%), possibly due to hyperthermia, P greater than 0.10. Using the combination of DHE plus light (photodynamic therapy) complete tumor regression was noted after a single treatment in 11 of 20 tumors (55%, mean tumor volume 279 mm3) and in 7 of 7 tumors (100%) after a second treatment. Two of 20 tumors were not retreated. Therefore, 18 of 20 tumors (90%) were grossly destroyed by one or two photodynamic treatments. Contralateral control tumors continued to grow to a median volume of 990 mm3 (chi 2 = 26.30, P less than 0.0001). Choriocarcinoma transplanted into the hamster cheek pouch is highly responsive to photodynamic therapy.
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PMID:Photodynamic therapy of choriocarcinoma transplanted to the hamster cheek pouch. I. Intraperitoneal photosensitization. 213 5

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

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

In continuation of the effort to delineate the structure of Photofrin, a chromatographically well separated component of the tumor-localizing fraction was isolated and purified using a combination of gel filtration chromatography and semi-preparative high-performance liquid chromatography. This component, the least hydrophobic of the tumor-localizing fraction, was deemed to be dihematoporphyrin ether, based on mass spectrometric analysis and its behavior toward base hydrolysis and lithium aluminum hydride reduction. Although less potent than Photofrin, the purified component was an active photosensitizer.
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PMID:Some components of the tumor-localizing fraction of hematoporphyrin derivative. 215 Aug 86

Photodynamic therapy is under intense investigation as an adjuvant treatment for malignant glial tumors of the central nervous system. Photofrin-II (HpD-II) is currently the most actively investigated photosensitizing agent. A crucial issue regarding the safe and efficacious usage of HpD-II-based photodynamic therapy is the individual in vivo kinetics of tumor uptake and retention, compared with normal brain clearance. The optimal time for photoactivation of sensitized tumor must be known to ensure a high target-to-nontarget ratio, resulting in the maximal tumor destruction while preserving normal brain. Our laboratory developed a radionuclide scan based on 111indium (111In)-labeled HpD-II to evaluate HpD-II localization and clearance noninvasively within a canine model of intracerebral gliosarcoma. Synthesis of the 111In-HpD-II complex in greater than 90% yield is achieved by a simple, rapid labeling method. Radiochemical purity and stability were verified by high-performance liquid chromatography. Using the canine model of intracerebral gliosarcoma, we followed the uptake of 111In-HpD-II in tumors with serial scintillation scanning. Localization of the tumor by 111In-HpD-II has been verified by contrast-enhanced computed tomographic scan followed by gross and histological examination of the enhancing brain region. Total body biodistribution of 111In-HpD-II at various times after injection has been evaluated. The ratio of uptake in tumor compared with surrounding brain peaked at 72 hours after injection. The knowledge of regional distribution and concentration of a photosensitizing agent within a tumor mass and surrounding brain allows for the most efficacious timing and localization of a photoactivating source.
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PMID:Indium-111-Photofrin-II scintillation scan. 252 21

Thirty patients with bladder carcinoma treated by photodynamic therapy (PDT) with hematoporphyrin derivative are presented. 24, 48 and/or 72 hours after intravenous injection of DHE 1.5-2.0 mg/kg or Y-HpD 5.0 mg/kg, the tumor was irradiated with 630 nm wavelength of argon dye laser via a quartz optic fibre inserted through the forceps channel of the cystoscope. Of the 30 patients treated, CR was obtained in 14 cases, PR in 13 cases and NR in 3 cases 1-3 months after therapy with a total effective rate of 90%. Among the 78 tumors found in the 30 cases, 52 were completely eradicated with a eradication rate of 66.7%. Photodynamic therapy is therefore useful in the treatment of transitional-cell carcinoma of the bladder. Yet, controlled trials are required to assess its place in the combined treatment of carcinoma of the bladder. Post PDT morphologic changes in the tumor, side effects, indication, advantages and disadvantages of this therapy are discussed.
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PMID:[Photodynamic therapy with hematoporphyrin derivative for transitional-cell carcinoma of the urinary bladder--report of 30 cases]. 253 89

Dihematoporphyrin ether, also known as Photofrin-II (Pf-II) is currently used in the diagnosis and management of a variety of epithelial neoplasms, in a modality known as photodynamic therapy (PDT). A major drawback of these porphyrins for PDT is their ability to evoke prolonged cutaneous photosensitization. The mechanism of tumor ablation and cutaneous photosensitization by these photosensitizers is thought to relate to the generation of one or more reactive oxygen species such as superoxide anion, singlet oxygen and hydroxyl radical. However, the role of these oxygen species has not been established unequivocally. In this study, the mechanism of Pf-II-mediated cutaneous photosensitization was examined using murine ear swelling as a marker. The mice treated with Pf-II and light demonstrated two-fold enhancement of ear swelling whereas animals treated with the SOD mimic, beta-carotene and dimethyl sulfoxide (DMSO) had considerably less ear swelling (p less than 0.01). The observed protective effect was dependent on the dose of each quencher and followed the pattern SOD mimic DMSO beta-carotene. The histopathologic alterations caused by Pf-II photosensitization were significantly alleviated by pretreatment with SOD mimic whereas beta-carotene and (DMSO) were less effective. Inhibitors of superoxide dismutase (sodium diethyldithiocarbamate) and catalase (hydroxyl amine and 3, amino 1,2,4-triazole) augmented Pf-II-mediated cutaneous photosensitization. These data provide the first in vivo evidence for the involvement of superoxide anion in cutaneous porphyrin photosensitization.
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PMID:In situ evidence for the involvement of superoxide anions in cutaneous porphyrin photosensitization. 283 53


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