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

High-dose chemotherapy and autologous bone marrow transplantation are an effective combination for treating a number of malignant disorders. Clinical trials have demonstrated a potential role for this regimen in the management of acute leukemia and non-Hodgkin's lymphoma. Autologous bone marrow transplantation continues to be limited by high relapse rates, as compared with allogeneic bone marrow transplantation. Two factors are thought to account for this observation. First, autologous transplants lack the immunologic "graft-versus-host" advantage of allogeneic transplants. Second, autologous grafts have the possibility of tumor cell contamination. Methods to reduce tumor cell contamination in autografts include exposure to chemical agents or monoclonal antibodies; long-term marrow cultures; and immunologic manipulation, either with immunomagnetic devices or antibody/complement combinations. Photodynamic therapy (PDT) with porfimer sodium (Photofrin; manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) or benzoporphyrin derivative (BPD verteporfin; BPD-MA; BPD-Quadra Logic Technologies, Inc, Vancouver, British Columbia, Canada) may be an effective means of purging bone marrow. The ability of malignant cells to selectively accumulate photosensitizing agents may account for efficacy of PDT in bone marrow purging. The efficacy of porfimer sodium and BPD has been evaluated in cell lines known to express multidrug resistance (MDR), and the results compared with corresponding MDR-negative cell lines. Multidrug resistance-positive cell lines appear relatively resistant to BPD; porfimer sodium remains active. The reason for the differential effect of MDR positivity on the cytotoxicity of porfimer sodium and BPD is unclear, but is believed to be related to the larger size of the porfimer sodium molecule. Clinical trials evaluating PDT in bone marrow transplantation are under way.
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PMID:The use of photodynamic therapy in bone marrow purging. 799 4

Photodynamic therapy (PDT) is based on the use of light-sensitive molecules called photosensitizers. Photoactivation causes the formation of singlet oxygen, which produces peroxidative reactions that can cause cell damage and death. Porfimer sodium (Photofrin, manufactured by Lederle Parenterals, Carolina, Puerto Rico, under license from Quadra Logic Technologies, Inc, Vancouver, BC, Canada) is the photosensitizer that has been studied most extensively. Patients generally have to be hospitalized for 2 days prior to light treatment after administration of porfimer sodium; it takes approximately 48 hours after injection to reach optimal concentration in tumor tissue. The tumoricidal capacity of PDT with porfimer sodium is determined in part by the maximum depth of penetration of light having a wavelength of 630 nm. Porfimer sodium causes cutaneous photosensitivity that may last for up to 6 weeks. Benzoporphyrin derivative (BPD verteporfin; BPD-Quadra Logic Technologies, Inc, Vancouver, BC, Canada), another photosensitizer, accumulates more rapidly in tumor tissue, permitting optimal PDT 30 to 150 minutes following intravenous administration. It is rapidly cleared from the body, and skin photosensitivity does not extend beyond a few days. The primary mechanism of action of PDT is related to the selective accumulation of photosensitizers in cancer tissue. Photodynamic therapy also shows promise in the treatment of a number of nonneoplastic conditions, including psoriasis, macular degeneration of the retina, atherosclerotic plaque and restenosis, bone marrow purging for treatment of leukemias with autologous bone marrow transplantation, inactivation of viruses in blood or blood products, and several autoimmune conditions, including rheumatoid arthritis. Physiologic characteristics shared by this disparate group of diseases, and the mechanisms by which they may mediate photoactivation, are discussed.
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PMID:Photosensitizers in photodynamic therapy. 799 5

Endoscopic thermal laser therapy of colorectal villous adenomas is associated with a high recurrence rate due to incomplete tumor ablation, as treatment over carries a risk of perforation. Photodynamic therapy has been shown to be a promising in the treatment of small malignant tumors, and may be useful for benign adenomas. Eight patients with nine colosigmoid villous adenomas measuring 1-5 cm in length were treated with photodynamic therapy using either haematoporphyrin derivative or Photofrin as photosensitizer and multiple (4-16) applications of interstitial photoirradiation with red light (630 nm, 100 mW x 500 s per application). All but one adenoma had previously been incompletely treated with Nd-YAG laser therapy. Some skin sensitivity to light was seen in one patient. Seven adenomas were eradicated (follow-up 9-56 months, median = 12) as judged by follow-up endoscopy and biopsy. No local complications were seen. Substantial necrosis was produced in the other two adenomas, but they were not completely destroyed, probably due to inadequate light. PDT holds promise in the non-surgical management of villous adenomas, particularly after initial tumour debulking with the Nd-YAG laser.
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PMID:Photodynamic therapy for villous adenomas of the colon and rectum. 802 74

Photodynamic therapy is a promising new modality for the treatment of neoplastic disease. Currently, Photofrin is the only photosensitizer approved for the treatment of human cancers. In the search for new, chemically pure second generation photosensitizing agents which absorb in the deep red region of the visible spectrum, a novel and unique photosensitizer, CDS1, an iminium salt of copper octaethylbenzochlorin, was developed. This new photosensitizer is chemically pure, cationic, and possesses a strong (epsilon = 35000 M-1.cm-1) absorption peak at 750 nm (in dichloromethane). With copper in the aromatic cavity and a triplet lifetime which is not measurable (< 20 nsec), the photodynamic activity of CDS1 was unexpected. Preliminary in vitro and in vivo animal studies with a transplantable urothelial tumor indicate that CDS1 is an effective photosensitizing agent when used in conjunction with a broad band xenon arc light source or a low frequency, high peak power pulsed alexandrite laser.
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PMID:Photodynamic therapy: a new modality for the treatment of cancer. 804 91

Photodynamic therapy (PDT) is a new, promising method in the treatment of cancer. To gain insights into PDT-mediated tumour destruction we studied the influence of treatment with Photofrin and laser light on changes in cell volume and cell viability. A-Mel-3 tumour cells were subjected to Photofrin or illumination with laser light, or a combination of both (PDT). Cell volume was measured by flow cytometry and cell viability by the trypan blue exclusion test for up to 60 min after PDT and the respective controls. In addition, scanning and transmission electron microscopy were performed. Tumour cells incubated in concentrations of 0.75, 1.5 and 3.0 micrograms Photofrin/ml revealed a rapid increase in cell volume to 117%, 207% and 235% 30 min after PDT and to 147%, 210% and 199% 60 min after PDT. Cell viability with 1.5 and 3.0 micrograms Photofrin/ml and laser light was reduced to 83% and 44% at 30 min after PDT and to 38% and 17% 60 min after PDT. At Photofrin concentrations of 1.5 micrograms/ml and exposure to laser light scanning electron microscopy revealed extreme loss of microvilli and formation of blebs on the cellular surface. Transmission electron microscopy showed swollen mitochondria and ruptures of the cell membrane. This study demonstrates that PDT induces a significant time-dependent and dose-related increase in tumour cell volume. We suggest that the PDT-induced swelling of tumour cells contributes to the increase of interstitial fluid pressure and to impairment of microvascular perfusion of tumours.
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PMID:[Damage to tumor cells by photodynamic therapy]. 816 10

Vascular stasis and tissue ischemia are known to cause tumor cell death in several experimental models after photodynamic therapy (PDT); however, the mechanisms leading to this damage remain unclear. Because previous studies indicated that thromboxane release is implicated in vessel damage, we further examined the role of thromboxane in PDT. Rats bearing chondrosarcoma were injected with 25 mg/kg Photofrin (intravenously) 24 h before treatment. Light (135 J/cm2, 630 nm) was delivered to the tumor area after injection of one of the following inhibitors: (1) R68070: a thromboxane synthetase inhibitor; (2) SQ-29548: a thromboxane receptor antagonist; and (3) Flunarizine: an inhibitor of platelet shape change. Systemic thromboxane levels were determined. Vessel constriction and leakage were evaluated by intravital microscopy. Tumor response was assessed after treatment. Thromboxane levels were decreased more than 50% with SQ-29548 as compared to controls. Thromboxane levels in animals given R68070 and Flunarizine remained at baseline levels. SQ-29548 and R68070 reduced vessel constriction compared to controls, while Flunarizine totally prevented vessel constriction. R68070 and SQ-29548 inhibited vessel permeability compared to PDT controls; Flunarizine did not. Animals given these inhibitors showed markedly reduced tumor cure. These results indicate that the release of thromboxane is linked to the vascular response in PDT.
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PMID:The effects of thromboxane inhibitors on the microvascular and tumor response to photodynamic therapy. 823 74

Very little is known about the applicability of the metabolic and biochemical events observed in cell culture systems to in vivo tumor shrinkage following photodynamic therapy (PDT). The purpose of this study was to assess whether PDT induces apoptosis during tumor ablation in vivo. We treated radiation-induced fibrosarcoma (RIF-1) tumors grown in C3H/HeN mice with PDT employing three photosensitizers, Photofrin-II, chloroaluminum phthalocyanine tetrasulfonate, or Pc IV (a promising phthalocyanine developed in this laboratory). Each photosensitizer was injected intraperitoneally and 24 h later the tumors were irradiated with an appropriate wavelength of red light using an argon-pumped dye laser. During the course of tumor shrinkage, the tumors were removed at 1, 2, 4 and 10 h post-PDT for DNA fragmentation, histopathologic, and electron microscopic studies. Markers of apoptosis, viz. the ladder of nucleosome-size DNA fragments, increased apoptotic bodies, and condensation of chromatin material around the periphery of the nucleus, were evident in tumor tissue even 1 h post-PDT; the extent of these changes increased during the later stages of tumor ablation. No changes were observed in tumors given photosensitizer alone or irradiation alone. Our data suggest that the damage produced by in vivo PDT may activate endonucleolysis and chromatin condensation, and that apoptosis is an early event in tumor shrinkage following PDT.
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PMID:Apoptosis during photodynamic therapy-induced ablation of RIF-1 tumors in C3H mice: electron microscopic, histopathologic and biochemical evidence. 830 97

The effects of aspirin (acetylsalicylic acid: ASA) on vessel behavior and tumor response were measured during and after photodynamic therapy (PDT). Changes to vessel constriction, macromolecular leakage, tumor interstitial pressure, and tumor response were examined. Animals were randomly placed into treatment groups and injected with 0-25 mg/kg Photofrin and given 0 or 135 J/cm2 light treatment. The light treatment was standardized to 75 mW/cm2 at 630 nm over a 30 min treatment interval (135 J/cm2). The treatment groups were further subdivided to receive Photofrin alone or Photofrin plus 100 mg/kg ASA. A cremaster muscle model in Sprague-Dawley rats was used to directly observe microvascular response and changes in vessel permeability to macromolecules. A tumor interstitial pressure model was designed to measure pressure changes in a chondrosarcoma tumor over time. This model indirectly measures macromolecular leakage, among other factors, in the tumor tissue. Groups of 10-20 rats were implanted subcutaneously with chondrosarcoma and were subjected to PDT to assess tumor response to the various treatments. Statistically significant differences in vessel leakage and changes in interstitial pressure were observed between animals given ASA plus PDT as compared to animals given PDT alone. The administration of ASA significantly inhibited venule leakage of albumin and reduced increases in interstitial pressure after treatment. The use of ASA had no effect on vessel constriction or tumor response after PDT. These findings suggest that the increases in vessel permeability observed during and after PDT, using Photofrin, do not significantly contribute to tumor response.
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PMID:The effects of aspirin on microvasculature after photodynamic therapy. 833 61

In this study the localisation of porphyrinoid photosensitizers in tumours was investigated. To determine if tumour selectivity results from a preferential uptake or prolonged retention of photosensitizers, intravital fluorescence microscopy and chemical extraction were used. Amelanotic melanoma (A-Mel-3) were implanted in a skin fold chamber in Syrian Golden hamsters. Distribution of the porphyrin mixture Photofrin and three porphycenes, pure porphyrinoid model compounds, was studied quantitatively by intravital fluorescence microscopy. Extraction of tissue and blood samples was performed to verify and supplement intravital microscopic results. Photofrin accumulated in melanomas reaching a maximum tumour:skin tissue ratio of 1.7:1. Localisation of the different porphycenes was found to be highly tumour selective (3.2:1), anti-tumour selective (0.2:1), and non-selective (1:1) with increasing polarity of the porphycenes. The two non-tumour selective porphycenes had distinctly accelerated serum and tissue kinetics; serum halflife times being as short as 1 min. The specific localisation of the slowly distributed, tumour selective photosensitizers, occurred exclusively during the distribution from serum and uptake into tissues. For the most selective porphycene, the tumour selection process had a halflife of 260 +/- 150 min and led to a strongly fluorescent tumour edge edema. Accumulation of porphyrines by the amelanotic melanoma (A-Mel-3) can be attributed to an enhanced uptake rate for lipophilic molecules in this subcutaneously growing neoplasm. The slow distribution of the two tumour specific photosensitizers and the strong fluorescence of these hydrophobic molecules in the tumour compartment with a high water content indicate a carrier role of serum proteins in the selection process. Enhanced permeability of the tumour vasculature to macromolecules appears to be the most probable reason for the tumour selectivity of these two sensitisers.
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PMID:Tumour localisation kinetics of photofrin and three synthetic porphyrinoids in an amelanotic melanoma of the hamster. 834 76

Photodynamic therapy (PDT) of cancer is an experimental tumor therapy which is based on the combined use of a systematically administered photosensitizer to a tumor-bearing host and local illumination of the lesion by a high-intensity visible light source, typically a tunable argon dye laser. Human squamous cell carcinoma (HSCC) is the most frequently encountered malignancy of the head and neck. In this study, responses of HSCC cells to PDT were examined in in vitro and in vivo systems. In in vitro studies, the HSCC cells showed a positive photodynamic response with Photofrin-II (Pf-II), chloroaluminum phthalocyanine tetrasulfonate (AlPcTS), and a newly synthesized silicon phthalocyanine (SiPc IV). Single cell suspension of HSCC injected subcutaneously on the back of athymic nude mice resulted in a well-circumscribed tumor mass. The animals required a low tumor dose for the successful establishment of a tumor. The tumor was minimally immunogenic and showed neither macroscopic signs of early metastasis to lung, kidney, liver, or spleen nor evidence of surrounding erythema, fluctuation, or tenderness until the late stages of necrosis. Intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing mice resulted in rapid uptake of the photosensitizers in liver, skin, and tumor tissue. Twenty-four hours following the intraperitoneal administration of AlPcTS or SiPc IV to tumor-bearing animals, the tumor to normal skin ratio of the photosensitizer was 1.6 or 1.5, respectively. Administration of Pf-II (5 mg/kg) to tumor-bearing animals followed 24 hours later by irradiation of the tumor (135 J/cm2, 630 nm light from an argon pumped-dye laser) resulted in greater than 80% ablation in tumor volume 24 hours post-PDT. These characteristics make this tumor model system suitable for PDT studies of human tumor cells in vitro as well as in vivo.
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PMID:Photodynamic therapy of human squamous cell carcinoma in vitro and in xenografts in nude mice. 836 17


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