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

Studies have shown that meta-tetrahydroxy-phenylchlorin is an efficient tumor targeting agent for laser photodynamic therapy. The effectiveness of this approach for cancer treatment depends on drug concentration, incubation time and extracellular protein. We studied uptake and retention kinetics of mTHPC in a human fibroblast cell line. Our results clearly demonstrate a difference in the amount of extracellular mTHPC at an incubation temperature of 37 degrees C compared to 20 degrees C and 4 degrees C. pH-values were always constant and not responsible for the increase. Furthermore, both absorption and fluorescence of mTHPC increase when incubated at normal human body temperature. Incubation of human fibroblast cells with mTHPC (10 micg/mL) showed that intracellular mTHPC increases in a linear manner reaching saturation after 24 hours and declining until 48 hours with concommitant increase of supernatant mTHPC. Therefore, we believe that tumor cells can be treated optimally with PDT following a delay > 24 hours after drug administration with a minimum of damage to surrounding normal tissues.
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PMID:A new approach to cancer therapy due to appropriate uptake and retention kinetics of meta-tetrahydroxy-phenylchlorin in a human fibroblast cell line. 893 40

Several parameters affect clinical trials in photodynamic therapy and influence the therapeutic outcome. Beside drug dose, light dose, drug-light interval and other variables, the fluence rate is a parameter that can influence the therapeutic results. In this study we have evaluated the fluence rate effect with a second-generation photosensitizer, tetra(m-hydroxyphenyl)chlorin (mTHPC) using a 7,12-dimethylbenz(a)anthracene induced early squamous cell carcinoma of the Syrian hamster cheek pouch as a tumor model. Following injection of 0.5 mg/kg of mTHPC, irradiation tests were performed at two drug-light intervals, 4 and 8 days. Wavelength and light dose were adapted from those applied routinely in clinical trials. Irradiations at 652 nm were carried out with fluences ranging from 8 to 20 J/cm2 delivered at fluence rates of 15 and 150 mW/cm2. Similar tests were also performed at 514 nm with a fluence of 80 J/cm2 delivered at fluence rates ranging from 25 to 125 mW/cm2. At both wavelengths and drug-light intervals for a given fluence, the higher fluence rates resulted in less tissue damage in tumor and healthy mucosae. However, the lower fluence rates yielded slightly less therapeutic selectivity. This study confirms that the fluence rate is of major importance in clinical PDT.
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PMID:In vivo fluence rate effect in photodynamic therapy of early cancers with tetra(m-hydroxyphenyl)chlorin. 897 39

Photosensitizer is known to spread with vasogenic edema fluid arising from a cerebral lesion (Neurosurg 33:1075-1082, 1993), which may be essential for sensitizing malignant cells outside the main tumor mass. The present experiments seek to elucidate whether resultant necrosis of perifocal brain tissue after laser irradiation follows a corresponding time pattern and whether damage depends on the photosensitizer dose. Male Wistar rats were anaesthetized with chloralhydrate for venous cannulation, craniotomy and focal cold lesion in order to induce vasogenic edema. Simultaneously, Photofrin II (PF II) was administered at a dose of 5 mg kg-1. The animals were re-anaesthetized after either 4, 12 or 24 h for the irradiation of lesion and perifocal tissue with 200 J cm-2 of laser light (630 nm). The brains of other animals were irradiated 4 h after cold lesion with 200 J cm-2 after receiving either 0, 2.5 or 5 mg kg-1 PF II (all groups: n = 6). Resultant necrosis was assessed planimetrically in serial coronal cryosections of brains perfusion fixed 24 h after irradiation. Necrosis was significantly enhanced with irradiation 4 h after cold lesion and photosensitizer (avg. area +/- SD: 4.3 +/- 0.7 mm2) compared with lesion only (0.84 +/- 0.2 mm2). Maximal necrosis (6.3 +/- 1.6 mm2) occurred with irradiation 12 h after lesion, whereas necrosis was only slightly increased with irradiation at 24 h (2.8 +/- 0.4 mm2). Furthermore, the area of necrosis was dependent on the sensitizer dose (0 mg kg-1: 0.7 +/- 0.3 mm2, 2.5 mg kg-1: 2.09 +/- 0.2 mm2, 5 mg kg-1: 4.3 +/- 0.7 mm2; all differences p < 0.05). Therefore, to prevent unwanted side-effects such as necrosis of edematous but otherwise healthy, peritumoral tissue in the treatment of malignant cerebral tumors by PDT, tribute should be paid to the possibility of time and dose dependent sensitization of the perifocal tissue after i.v. administration of photosensitizer.
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PMID:Photodynamic therapy within edematous brain tissue: considerations on sensitizer dose and time point of laser irradiation. 900 56

In vivo experiments were performed to evaluate the effect of fluence rate on the efficiency of Zn(II)-2,3 naphthalocyanine (ZnNc) photosensitization of B16 pigmented melanoma subcutaneously transplanted in C57B1/6 mice. The tumour was irradiated with 774 nm light at 24 h after an injection of liposome--which incorporated ZnNc (0.5 mg kg-1 b.w.). A total light dose of 360 J cm-2 was delivered at fluence rates of 260, 320, 380, 440 and 500 mW cm-2. Separate groups of mice utilized to monitor tumour temperature changes during irradiation without or after anaesthesia. Tumour response was determined by measuring the mean tumour diameter of the treated towards the untreated animals for a period of 21 days following PDT, as well as the percentage of cured animals. The most promising result (40% complete tumour response) was obtained with anaesthetized mice following 380 mW cm-2. Higher dose rates (440 and 500 mW cm-2) led to less promising results for both anaesthetized and non anaesthetized mice. These results outline the potential of PDT with longer wavelengths for the treatment of highly pigmented tumour tissues. The optimal fluence rate for tumour treatment should be chosen in order to avoid inflammatory effects (tissue swelling) and oxygen suppression with sublethal injury to the tumour cells.
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PMID:Fluence rate effects on photodynamic therapy of B16 pigmented melanoma. 904 2

Aminolevulinic acid (ALA) is being used as a "prodrug" for photodynamic therapy. The side effects of ALA have been only anecdotally reported and these effects as well as pharmacokinetics of the photosensitizing end product of ALA, protoporphyrin IX (PpIX), in patients undergoing operation are unknown. This study systematically determines the side effects of ALA and pharmacokinetics of PpIX in patients undergoing abdominal surgery. Patients were given 30 or 60 mg/kg ALA preoperatively, kept in subdued light for 48 hr, and monitored clinically and with laboratory tests for 5 to 7 days and for at least 2 months thereafter. Periodic plasma samples and tissue biopsies were analyzed for PpIX concentrations using a photodiode array system. No patient developed symptoms of porphyria other than nausea and vomiting, which occurred in 20%. Nearly one-quarter of patients developed transient abnormal liver functions. No patient developed cutaneous phototoxicity, abnormal neurologic function, or unexpected postoperative laboratory tests. The times of peak plasma, skin, skeletal muscle, omental, mucosal, muscularis mucosal, and tumor concentrations of PpIX varied among patients. In general, PpIX concentrations were significantly greater with the higher dose of ALA. Tumor PpIX concentrations were significantly greater than in other tissues except liver. In conclusion, ALA, up to 60 mg/kg, is associated with minimal side effects in patients undergoing operation. Actual tissue concentrations of PpIX suggest that endogenous photosensitization using systemically administered ALA is a mode of PDT feasible for treatment of adenocarcinomas of the gastrointestinal tract in humans.
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PMID:Side effects and photosensitization of human tissues after aminolevulinic acid. 912 92

The efficiency of a new photosensitizer of the second generation, meso-tetra-hydroxyphenyl-chlorin (mTHPC), which has a strong absorption at 652 nm, was investigated by oxygen consumption measurements and membrane integrity testing. The experiments proved a great increase in the efficiency of mTHPC after preincubation at 37 degrees C for 24 hours. From these findings it can be assumed that tumor cells can be treated in an optimal way with PDT after a longer delay following drug administration.
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PMID:Does the in-vitro efficiency of meso-tetrahydroxy-phenyl-chlorin depend on pre-treatment of sensitizer? 920 88

A versatile PDT light dosimetry model is described incorporating the effects of drug photobleaching, drug elimination, and normal tissue damage. The dependence of the necrosis depth (dn) on the incident light dose for the four major modes of PDT light delivery has the form: dn = delta loge(DG), where delta is the optical penetration depth of the tumor tissue, D is the ratio of the incident light dose to the energy fluence at the necrosis threshold, and G is a function of the tissue optical constants. Light dosimetry graphs were calculated for Photofrin at standard conditions.
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PMID:PDT light dosimetry revisited. 920 89

Studies on the synthesis, preliminary in vivo biological activity, singlet oxygen and fluorescence yields of a dimeric porphyrin (D1) are described. The pharmacokinetic behavior and photodynamic properties of the dimer D1 were examined in Balb/c mice bearing an MS-2 fibrosarcoma. Compound D1 shows a high selectivity for tumor localization (tumor/peritumoral tissue ratios of dye concentration ranging between ca 100 and 140 at 24 h after drug administration of 5.0-1.0 mg kg-1 into DL-alpha-dipalmitoylphosphatidylcholine liposomes). The phototherapeutic efficiency of dimer D1 was evaluated by following the growth curves of fibrosarcoma irradiated with red light (600-700 nm) with a total dose of 400 J cm-2, at 24 h after intravenous injection. Photodynamic therapy-treated tumors showed a significant delay in growth as compared to untreated control mice. The results obtained suggest that the porphyrin dimer D1 may be a promising candidate for further use in PDT experiments.
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PMID:Meso-tetraphenylporphyrin dimer derivative as a potential photosensitizer in photodynamic therapy. 933 11

9-acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn) is a chemically pure substance with fast pharmacokinetics and superior photodynamic properties in vitro as compared to Photofrin. In this study the pharmacokinetics, photodynamic efficacy and tissue localization of ATMPn were investigated in vivo. Amelanotic melanomas (A-Mel-3) were implanted in dorsal skin fold chambers fitted to Syrian Golden hamsters. Fluorescence kinetics of ATMPn (1.4 mumol kg-1 b.w.i.v.; n = 8) were monitored by intravital microscopy. Quantitative measurements of fluorescence intensity were carried out by digital image analysis. For tumor growth studies 1.4 mumol kg-1 was injected 24 h (n = 3), 3 h (n = 3), 1 min (n = 6) and 2.8 mumol kg-1 1 min (n = 6) before PDT (Laser (630 nm) or lamp (600-750 nm), 100 mW cm-2, 100 J cm-2). Tumor volume was measured for 28 d. Solid tumors (n = 3) were excised 1 min after injection of ATMPn (2.8 mumol kg-1) and cryostat sections (20 mm) were analyzed by confocal laser scanning microscopy (CLSM) for tissue localization of the dye. Maximal fluorescence (mean +/- S.E.) arose in the tumor (94 +/- 7%) and surrounding host tissue (67 +/- 5%) 30 s post injection followed by a rapid decrease. Hardly any fluorescence was detectable 12 h after administration. Only PDT 1 min after injection of ATMPn was effective yielding 3/6 complete remissions (2.8 mmol kg-1, laser) and 6/6 complete remissions (2.8 mumol kg-1, lamp), respectively. One minute after injection the dye is primarily localized in the vascular wall of normal and tumor vessels as shown by CLSM. PDT at a time, when the dye is localized primarily in the tumor microcirculation, exhibits the best tumor killing effects showing that vascular targeting is effective in treating solid malignant tumors. ATMPn in liposomes makes administration and light irradiation in one session possible due to its fast pharmacokinetics. Thus, using ATMPn as a photosensitizer may provide more flexibility to perform PDT after surgical exploration and debulking as adjuvant therapy.
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PMID:Targeting of the tumor microcirculation by photodynamic therapy with a synthetic porphycene. 937 21

The use of endogenously created porphyrins as an alternative to photosensitizer injection for photodynamic therapy is a rapidly evolving area of study. One common method to induce porphyrin synthesis and accumulation in cells is the topical, oral, or parenteral administration of 5-aminolevulinic acid, a precursor for heme biosynthesis. Porphyrin accumulation may also be elicited by the use of enzyme inhibitors of the heme biosynthetic pathway. Groups of DBA/2 mice bearing SMT-F mammary tumors were placed on a diet containing 0-4000 ppm of a protoporphyrinogen oxidase inhibitor, FP-846. This agent blocks a critical step in porphyrin metabolism and results in elevated intracellular levels of protoporphyrin IX. Light treatment of tumors produced both initial and long-term regression that was dependent on the amount of inhibitor, the duration of inhibitor exposure to animals, and the amount of light used in PDT. Tumor regression occurred without significant destruction of normal tissues in the treatment field and without initial vascular constriction or blood flow stasis. Tumor cure in animals given 4000 ppm FP-846 in feed for 3 days and 300 J/cm2 602-670 nm light (23% cure) was similar to the response in animals given 10 mg/kg Photofrin and the same light dose (20%).
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PMID:Photodynamic therapy using a protoporphyrinogen oxidase inhibitor. 937 68


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