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)

Alpha-tocopherol at low concentrations protects biosubstrates from oxidative damage, while at high concentrations it may become toxic. Certain lines of tumor cells are reported to contain higher levels of vitamin E than normal cells. In our study alpha-tocopherol was successfully incorporated by cultured HT29 adenocarcinoma cells, but not by MRC-5 normal fibroblasts. At high concentrations (0.3-1 mM) alpha-tocopherol enhanced meta-tetra(hydroxyphenyl)chlorin (mTHPC)-sensitized photoinactivation of HT29 cells (415 nm), but not that of normal fibroblasts. At none of the concentrations used (0.001-1 mM) did alpha-tocopherol protect cells from photokilling, indicating that lipid peroxidation is of minor importance in mTHPC photoactivity. Our findings encourage the in vivo testing of phenolic antioxidants for selective enhancement of PDT-damage in tumors.
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PMID:Meta-tetra(hydroxyphenyl)chlorin-sensitized photodynamic damage of cultured tumor and normal cells in the presence of high concentrations of alpha-tocopherol. 1040 14

Primary small cell carcinoma of the esophagus is a rare and aggressive disease. We report on our experience with two patients having a small cell cancer of the esophagus, being treated with photodynamic therapy combined with irradiation and induction-chemotherapy as well as a review of literature. Both patients were admitted with severe dysphagia, weight loss and a Karnovsky performance status of 90. Diagnostic work-up revealed tumor-stenosis in the proximal third in one and in the distal third in the other case. Clinical staging showed T4N2M0 and T3N2M0, pure small cell carcinoma. Due to dysphagia and lymph node enlargement, local and systemic therapy were considered as first-line treatment. Restaging after three cycles of induction-chemotherapy revealed partial response in both cases. Esophagectomy as a second-line treatment was considered. However, in the preoperative period, one patient developed motorical aphasia. The CT-scan of the brain showed multiple brain metastases. External beam irradiation and further chemotherapy was initiated. The patient died 12 months after admission. The other patient revealed anatomical inoperability at the staging laparoscopy. External beam irradiation and a second session of PDT was performed. The patient is still alive, 12 months after his first admission. The biological behavior of this aggressive disease and metastases in about 50% of patients at admission, as well as significant dysphagia makes combined systemic and local treatment necessary. Nevertheless, after reviewing the literature, esophagectomy and adjuvant chemotherapy may have an advantage pertaining to survival time when anatomical and functional operability is given.
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PMID:Local and systemic treatment in small cell carcinoma of the esophagus. 1060 16

This article addresses experimental investigations and the clinical use of PDT in the Rudolfstiftung Hospital, Vienna. We investigated mesotetrahydroxyphenylchlorine (mTHPC) and the photosensitizer hematoporphyrin derivative alone or in combination to prove photodynamic antibacterial effects on Staphylococcus aureus (wild type). mTHPC showed antibacterial toxicity in the dark; hematoporphyrin derivative showed suppressive growth effects only after white-light illumination. Photodynamic activity by the combination of both dyes was obtained in a roughly additive manner. Furthermore, we observed the development of resistance of erythromycin after the illumination procedure with hematoporphyrin derivative. Wild-type S. aureus developed no resistance to the other antibiotics tested. Furthermore, long-term follow-up examinations proved mTHPC-mediated PDT as a possible adjuvant intraoperative therapy in cases of relapses of gynecologic carcinomas. PDT is a tissue-selective and simple intervention. It shows few side effects, and, therefore, it reduces the overall burden of tumor patients. In another clinical investigation, we used 5-aminolevulinic acid-based PDT to treat intraepithelial neoplasia and human papillomavirus of the uterine cervix. 33 of 38 (86,8%) patients with superficial cervical intraepithelial neoplasia grades I and II were treated successfully with PDT. Eradication of human papillomavirus infections was successfully performed in 80% of the cases.
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PMID:[Experimental investigations and clinical use of photodynamic therapy (PDT) in the Rudolf Foundation Hospital]. 1062 88

Photodynamic (PDT) therapy is a relatively new technique with unique properties that make it attractive for the local treatment of superficial epithelial disorders. The objective of this study was to investigate the clinical response of PDT with the photosensitizing agent 5-aminolevulinic acid (5-ALA) in patients with vulvar intraepithelial neoplasia (VIN) grades 1 to 3. Twenty-five patients with 111 lesions of VIN 1-3 were topically sensitized with 10 ml of a 20% solution of 5-ALA and treated with 57 cycles of laser light at 635 nm (100 J/cm(2)). Seventy (64%) of the 111 VIN lesions regressed after various PDT cycles. A complete response was achieved in 13 patients (52%) with 27 lesions. All patients with VIN 1 and mono- and bifocal VIN 2-3 showed complete clearance. However, a complete response could be achieved in only 4 (27%) of 15 women with multifocal VIN 2-3, whereas a partial response was noted in 9 of these patients with a total of 70 lesions, out of which 44 (63%) lesions disappeared. No response was seen in 2 patients with multifocal VIN 3. Histological assessment of the fluorescence-directed biopsies revealed that increased pigmentation and hyperkeratosis of the lesions were associated with low response rates. PDT using 5-ALA represents an alternative treatment modality for VIN which is easy to perform and has the advantage of minimal tissue destruction, low side effects and excellent cosmetic results. However, multifocal VIN disease with pigmented and hyperkeratinic lesions remains difficult to treat.
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PMID:Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid. 1069 44

Studies on the synthesis, singlet oxygen and fluorescence yields and pharmacokinetic properties of three different dimeric porphyrins with an amide linkage (D2-D4) are described and compared with the results recently reported for a dimeric porphyrin (D1). The pharmacokinetic behavior of all dimers were examined in Balb/c mice bearing MS-2 fibrosarcomas. The maximal efficiency and selectivity of photosensitizer accumulation in each tumor tissue takes place at 24 h after drug administration of 1.0 mg kg-1 into DL-alpha-dipalmitoylphosphatidylcholine liposomes by intravenous injection. Since the dimeric porphyrins exhibit high quantum yields of singlet oxygen generation, long triplet lifetimes and high photostability, the results obtained suggest that the evaluated dimeric structures may be promising candidates for further use in PDT experiments. The results also allow the possibility to establish a correlation between the chemical structure of the dyes and the efficiency/selectivity of the tumor accumulation and can be used for building up optimal photosensitizing agents for tumors.
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PMID:meso-tetraphenylporphyrin dimer derivatives as potential photosensitizers in photodynamic therapy. Part 2. 1094 76

Acridine orange (AO) has unique biological actions enabling tumor visualization (fluorovisualization) and a strong cytocidal effect (photodynamic therapy: AO-PDT) under illumination with blue light. Accordingly, in this study, we attempted to develop a new surgical technique for total tumor cell elimination using these photodynamic reactions with AO in a mouse osteosarcoma model. The results showed that local tumor recurrence was significantly inhibited (23%) in the group treated with curettage under fluorovisualization and AO-PDT, compared to that (80%) in the control group treated with curettage alone under ordinary light. Therefore, we concluded that the combination of curettage under fluorovisualization and AO-PDT may be useful for total tumor cell elimination with minimum damage to normal tissue in musculoskeletal sarcomas.
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PMID:Total tumor cell elimination with minimum damage to normal tissues in musculoskeletal sarcomas following photodynamic therapy with acridine orange. 1097 Nov 78

This paper describes the photodynamic characteristics of the new near-infrared photosensitizer 5,10,15,20-tetrakis(m-hydroxyphenyl)bacteriochlorin (mTHPBC or SQN400) in normal rat and mouse tissues. A rat liver model of photodynamic tissue necrosis was used to determine the in vivo action spectrum and the dose-response relationships of tissue destruction with drug and light doses. The effect of varying the light irradiance and the time interval between drug administration and light irradiation on the biological response was also measured in the rat liver model. Photobleaching of mTHPBC was measured and compared with that of its chlorine analog (mTHPC) in normal mouse skin and an implanted mouse colorectal tumor. The optimum wavelength for biological activation of mTHPBC in rat liver was 739 nm. mTHPBC was found to have a marked drug-dose threshold of around 0.6 mg kg-1 when liver tissue was irradiated 48 h after drug administration. Below this administered drug dose, irradiation, even at very high light doses, did not cause liver necrosis. At administered doses above the photodynamic threshold the effect of mTHPBC-PDT was directly proportional to the product of the drug and light doses. No difference in the extent of liver necrosis produced by mTHPBC was found on varying the light irradiance from 10 to 100 mW cm-2. The extent of liver necrosis was greatest when tissue was irradiated shortly after mTHPBC administration and necrosis was absent when irradiation was performed 72 h or later after drug administration, suggesting that the drug was rapidly cleared from the liver. In vivo photobleaching experiments in mice showed that the rate of bleaching of mTHPBC was approximately 20 times greater than that of mTHPC. It is argued that this greater rate of bleaching accounts for the higher photodynamic threshold and this could be exploited to enhance selective destruction of tissues which accumulate the photosensitizer.
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PMID:In vivo photodynamic characteristics of the near-infrared photosensitizer 5,10,15,20-tetrakis(M-hydroxyphenyl) bacteriochlorin. 1098 7

Hypericin, a polycyclic quinone obtained from plants of the Hypericum genus, exhibits strong photodynamic antitumor effects. In the present study, PDT efficacy of hypericin under different conditions was compared in a P388 mouse tumor model. Plasma and tumor drug measurements and assessment of vascular damage by fluorescein dye exclusion were performed to determine the relative contributions of vascular effects and direct tumor cytotoxicity. Furthermore, the influence of modifying tumor oxygenation on PDT effect was also evaluated. Study of PDT efficacy and tissue distribution revealed that PDT efficacy was more dependent on plasma concentration than tumor drug level. Fluorescein dye exclusion indicated the complete microvascular occlusion in the tumor and surrounding skin immediately after effective PDT treatments, while only a limited vascular occulation was observed after non-effective PDT treatment. It was found that neither tumor hypoxia induced by hydralazine nor increasing tumor oxygenation achieved by nicotinamide could significantly affect the effectiveness of various PDT protocols. These results suggest that tumor vasculature damage might be the primary mechanism of hypericin-mediated PDT effect. The existence of this potent secondary vascular effect is likely to account for the inability of tumor oxygenation modifiers to affect tumor response after PDT with hypericin.
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PMID:Photodynamic therapy with hypericin in a mouse P388 tumor model: vascular effects determine the efficacy. 1125 Nov 68

Starting from methylpheophorbide-a, a homologous series of purpurinimides containing alkyl substituents at two different positions [as 3-(1(1)-O-alkyl) and 13(2)-N-alkyl] were synthesized. These compounds with variable lipophilicity (log P 5.32-16.44) exhibit long wavelength absorption near lambda(max)700 nm (epsilon: 45 000 in dichloromethane) with singlet oxygen ((1)O2) production in the range of 57-60%. The shifts in in vivo absorptions and tumor/skin uptake of these compounds were determined in C3H mice bearing RIF tumors by in vivo reflectance spectroscopy. The results obtained from a set of photosensitizers with similar lipophilicity (log P 10.68-10.88) indicate that besides the overall lipophilicity, the presence and position of the alkyl groups (O-alkyl vs N-alkyl) in a molecule play an important role in tumor uptake, tumor selectivity, and in vivo PDT efficacy. At present, all purpurinimide analogues are being evaluated at various doses, and experiments are underway to establish a quantitative structure-activity relationship on a limited set of compounds. The 1D and 2D NMR and mass spectrometry analyses confirmed the structures of the desired purpurinimides and the byproducts formed during various reaction conditions. The mechanisms of the formation of the unexpected 12-formyl- and 12-(hydroxymethyl)purpurinimides under certain reaction conditions are also discussed.
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PMID:Synthesis, photophysical properties, tumor uptake, and preliminary in vivo photosensitizing efficacy of a homologous series of 3-(1'-alkyloxy)ethyl-3-devinylpurpurin-18-N-alkylimides with variable lipophilicity. 1133 64

We investigated the hypericin-mediated PDT effects on the tumor and normal skin and in correlation with its biodistribution. These studies were carried out on C3H mice bearing RIF-1 tumors. The hypericin distribution and PDT effects were recorded at different intervals (0.5-24 hr) after intravenous injection of a 5-mg/kg dose of hypericin. After administration, rapid biphasic exponential decay was observed in the plasma drug concentration. It was found that hypericin was preferentially bound to the plasma lipoproteins. The tumor drug levels increased rapidly over the first few hours and reached a maximum around 6 hr after injection. In contrast, PDT efficacy was maximal when irradiation was performed at 0.5 hr after hypericin administration, which led to 100% cure. The PDT efficacy decreased rapidly as the administration-irradiation interval was prolonged. No tumor cure was obtained at the 6-hr interval, even though it was at this time that the tumor drug level peaked. Fluorescence microscopic studies showed that hypericin was mainly confined within the tumor vasculature at 0.5 hr after injection, whereupon it rapidly diffused to the surrounding tumor tissue. At 6 hr, a strong hypericin fluorescence was observed in the tumor tissue with only faint fluorescence within the vasculature, whereas at 24 hr the fluorescence in the tumor also decreased and became more diffused, and no fluorescence could be seen in the tumor vasculature. Like the tumor response, skin reactions were also found to be much more dramatic at short administration-irradiation intervals. Hypericin distribution and PDT response studies revealed a close correlation between the plasma drug level and the PDT effects, which suggests that vascular damage is the primary effect of hypericin-mediated PDT in this tumor model.
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PMID:Efficacy of antitumoral photodynamic therapy with hypericin: relationship between biodistribution and photodynamic effects in the RIF-1 mouse tumor model. 1141 Aug 77


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