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)

Four structural analogs of benzoporphyrin derivative (BPD), a potent anti-tumor photosensitizer, were evaluated for their capacity to influence the immunologically-mediated contact hypersensitivity (CHS) response against the hapten 2,4-dinitrofluorobenzene (DNFB). Immunocompetent hairless strain mice received BPD monoacid ring A (BPD-MA, verteporfin) and returned to normal housing conditions or treated with 690 nm red light (transcutaneous photodynamic therapy, PDT). Unexpectedly, we found that mice given BPD-MA exhibited significantly reduced CHS ear swelling responses to DNFB upon antigenic challenge, whether or not they had been treated with PDT. A significant reduction in the CHS response to DNFB was observed when BPD-MA or PDT was given 48 or 24 h prior to, on the same day, or 24 or 72 h after DNFB sensitization. However, the magnitude of the CHS response was unaffected if these treatments were given 96 h after DNFB sensitization, 24 h before challenge with DNFB. Significantly reduced CHS responses also occurred in Balb/c mice given BPD-MA with or without PDT. Mice given BPD-MA but retained in total darkness throughout the experimental period generated full-fledged ear swelling responses to DNFB indicating that CHS suppression with BPD-MA was light dependent. BPD monoacid ring B (BPD-MB) strongly reduced the CHS response of Balb/c mice kept under ambient light while BPD diacid ring A (BPD-DA) and BPD diacid ring B (BPD-DB) also lowered the CHS response but were less effective than the monoacid forms. Other photosensitizers including Photofrin, tin etiopurpurin, and zinc phthalocyanine did not alter the CHS response of Balb/c mice maintained under ambient light. The ability of different BPD analogs to inhibit the CHS response in mice held under ambient light conditions appears related to the potent photosensitizing activity of these compounds.
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PMID:Inhibition of contact hypersensitivity with different analogs of benzoporphyrin derivative. 940 41

Tumor sensitivity to cancer therapies may be modulated by the p53 status of the malignant cells. Generally, tumors retaining wild-type p53 are more sensitive to radiotherapy and some chemotherapeutic agents than are tumors with either a mutated or deleted p53 phenotype. The role of p53 in the responsiveness to PDT as a cancer treatment is clinically unknown. In the current study, we evaluated the photosensitivity of two human colon carcinoma cell lines, one expressing wild-type p53 protein and the other expressing mutant p53. Wild-type p53 cells were found to be significantly more sensitive to Photofrin-mediated photodynamic treatment measured by clonogenic assay. Uptake of the photosensitizer was equivalent for both cell lines. Interestingly, sensitivity of the colon carcinoma cell lines to ionizing radiation was similar. These two cell lines represent a useful model for examining p53 involvement in the cellular response to PDT-mediated oxidative stress.
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PMID:Differential photosensitivity in wild-type and mutant p53 human colon carcinoma cell lines. 954 Feb 17

Benzoporphyrin derivative (BPD) is a potent photosensitizer in biological systems. There are four structural analogues of BPD. The analogues share the same chromophor, which results in their having almost identical optical spectra, extinction coefficients, and yields of singlet oxygen. Small structural differences affect their photosensitizing potency in various biological systems, and thus make them an interesting tool to study the structure-activity relationship. The ranking of the photosensitizing potency of the analogues differed depending on the test system. The more efficient photosensitization of tumor cell lines by the highly lipophilic monoacids as compared to that by less lipophilic diacids correlated positively with the partition coefficient, and was related to the rate of diffusion into the cells. However, in the assay systems where PDT targets were located in the membrane (red blood cells hemolysis, enveloped vesicular stomatitis virus, isolated mitochondria) there was very little difference in photosensitizing potency of BPD analogues. The results indicate that the evaluation of photosensitizers is affected by the test system and thus for photosensitizers screening purposes, the choice of the test system should be made based on the intended ultimate use.
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PMID:Photosensitizing potencies of the structural analogues of benzoporphyrin derivative in different biological test systems. 961 1

The photodynamic effects of m-tetrahydroxyphenylchlorin (mTHPC) were assessed on human malignant mesothelioma, squamous cell carcinoma and adenocarcinoma xenografts grown in nude mice and were correlated with mTHPC uptake, histology and doubling time of the tumors. Non-thermal laser light was delivered to the tumor as surface radiation 4 days after intraperitoneal administration of 0.1 and 0.3 mg mTHPC/kg body weight, respectively. The extent of tumor necrosis was measured by histomorphometry. The mTHPC concentration in non-irradiated tumors was assessed by high-performance liquid chromatography (HPLC). The tumors were graded according to their doubling time and their vascular architecture as assessed by histology. The 0.1 mg/kg dose of mTHPC resulted in an equal uptake for all 3 tumor types but revealed a larger extent of photosensitized necrosis for adenocarcinoma, which displayed a delicate tumor stroma with numerous small capillary vessels, than for mesothelioma and squamous cell carcinoma, which were both poor in stroma and vessels. The 0.3 mg/kg dose of mTHPC resulted in a 2-fold higher tumor uptake for all 3 tumor types and in a larger extent of necrosis for mesothelioma and squamous cell carcinoma, but not for adenocarcinoma xenografts, compared with the lower drug dose. Our results demonstrate that different tumor xenografts respond differently to mTHPC-PDT for a given drug-light condition. In this setting, the photosensitizing effect was more closely related to the vascular architecture of the tumors than to the sensitizer uptake and doubling time of the different tumors
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PMID:Photosensitizing effects of m-tetrahydroxyphenylchlorin on human tumor xenografts: correlation with sensitizer uptake, tumor doubling time and tumor histology. 962 55

Irradiation of B16 pigmented melanoma subcutaneously transplanted in C57 mice with a single 650 mJ pulse (10 ns) of 1064 nm light from a Q-switched Nd: YAG laser caused instantaneous bleaching of the pigmented tissue. Visual and histological examination of the resulting gray-colored tumor revealed the breakdown of melanosomes with no detectable alteration of the normal and tumor-overlying skin. Histological examination of the irradiated tumor showed some degree of vascular damage; the depth of the photodamage was not affected by the successive delivery of three consecutive light pulses. The bleached tumor grew at a modestly slower rate but the high-peak-power (HPP) laser treatment did not affect the tumor concentration of a photodynamic sensitizer Si(i.v.)-naphthalocyanine (isoBO-SiNc) intravenously injected 24 h before Nd:YAG irradiation. Treatment of the B16 pigmented melanoma by photodynamic therapy (PDT: 1 mg/kg isoBO-SiNc, 300 mW/cm2, 520 J/cm2) from a 774 nm diode laser immediately after the 1064 nm irradiation resulted in a 16 day delay of tumor regrowth, which was markedly longer than the delay (ca 6 days) obtained after PDT under identical conditions without the preirradiation. Thus, pretreatment of pigmented tumors with HPP 1064 nm light appears to enhance their susceptibility to conventional PDT. The tumor response was further enhanced by repeating the combined HPP/PDT treatment at an interval of 10 days (regrowth delay: 27 days), as well as by applying hyperthermia immediately after HPP/PDT (regrowth delay: ca 34 days).
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PMID:Treatment of malignant melanoma by high-peak-power 1064 nm irradiation followed by photodynamic therapy. 974 92

Benzochlorin iminium salts (BIs) are hydrophobic photosensitizers based on an octaethylbenzochlorin nucleus that absorb in the near-IR region of the visible spectrum. In these studies the photodynamic activities of the zinc, copper and metal-free BI derivatives were compared in vivo in C3H-HeJ mice bearing a mammary adenocarcinoma tumor line. In vitro studies were also performed with the radiation-induced fibrosarcoma tumor line. An argon-pumped Ti-sapphire laser tuned to deliver light between 710 and 800 nm or an Oriel arc-lamp filtered to deliver broadband light above 590 nm were used as light source. A lipid emulsion was used as the delivery system for sensitizers in all studies. A pronounced solvent dependence was observed for the Q band for each of all iminium salts examined. As an example, the metal-free (BI) derivative had an absorption maximum at 798 nm in dichloromethane and at 727 nm in serum. The action spectra showed a greater PDT response at blue-shifted wavelengths for each of the three iminium salts both in vivo and in vitro. Among the three derivatives, the zinc analog (ZnBI) produced the greatest tumor regression at the low drug/light dose of 0.7 (mumole/kg and 200 J/cm2. These results indicate that iminium salts have characteristics that may make them promising third-generation photosensitizers.
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PMID:In vivo and in vitro photodynamic studies with benzochlorin iminium salts delivered by a lipid emulsion. 979 39

Bacteriochlorin a photodynamic therapy (BCA-PDT) caused inhibition of interleukin (IL)-8-activated neutrophil migration, at concentrations that did not induce membrane damage. Random migration and migration induced by other chemoattractants were also inhibited, indicating that the effect of BCA-PDT was not at the level of chemoattractant-receptor interaction but down stream. The BCA-PDT completely blocked superoxide production of phorbol ester-stimulated neutrophils indicating that superoxide production by neutrophils present in the tumor before and during BCA-PDT is not the cause of inactivation of tumor cells. Both type I and type II quenchers prevented inhibition by BCA-PDT but only in electroporated cells. Confocal laser scanning microscopy showed that the fluorescence of BCA was located inside the cell. These results show that the effects of BCA-PDT are intracellular and of a mixed type I/type II character and that the neutrophils present in the tumor during illumination probably do not contribute to tumor eradication by releasing reactive oxygen species.
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PMID:The effects of photodynamic therapy on human neutrophil migration using bacteriochlorin a. 986 34

Photochemotherapy (PCT) consists in administration of a photosensitizer and subsequent irradiation of the tumor with visible light. Routinely, the photosensitizer is given intravenously (i.v.), but the major drawback of this procedure is the resulting skin photosensitivity. The goal of our study is to examine whether intravesical (i.b.) instillation of the photosensitizer for PDT of bladder cancer might be feasible in order to target the tumors and to avoid the photosensitization phenomenon. After first studying the biodistribution of hematoporphyrin derivative (HpD) in vivo in the rat bladder, two and four hours after intravesical administration, by fluorescence microscopy, we compared two different methods for the induction of superficial bladder tumors in rats with AY-27 tumor cell line in order to perform the same study on bladder tumors. The best results for the penetration depth of HpD in the normal bladder wall were obtained two hours after the bladder instillation where the photosensitizer was detected only in the bladder surface (urothelium and small part of the chorion). That's why we must choose the most appropriate bladder tumor model in order to obtain superficial bladder tumors that mimic the clinical behavior of superficial bladder cancer in man. Both techniques used in this study gave a high tumor take rate in a short time (> 90%). But we really obtained superficial bladder tumors directly attached to the bladder surface with one of the two methods of tumor induction consisting in the abrasion of the bladder surface prior to the administration of the tumoral cells in the bladder cavity.
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PMID:Induction of superficial bladder tumors in the female Fischer 344 rats with AY-27 tumor cells for the study of diffusion and localization of hemoglobin derived components (hematoporphyrin derivative) in view of photochemotherapy. 1006 40

One hundred forty-two patients with advanced gastrointestinal cancers were treated by PDT from September 1982 to December 1988. Hematoporphyrin derivative (HpD) (5 mg/kg) was given intravenously 48-72 hours before PDT. The light source was an argon dye laser with an output beam of 630 nm. The entire tumor was irradiated with a light dose of 100-250 J/cm 2. Fifteen patients (10.6%) had a complete response, 53 (37.3%) had a partial response, and 32 (22.5%) had a mild response. In all, 100 patients (70.4%) had a response to PDT. The experiments and clinical results show that the estimated energy dose (EED) value 200-250 J/cm 2 is appropriate. All patients were treated by PDT and adjuvant chemotherapy and showed good results with a follow-up of 1-5 years. Thirteen of 15 patients in the CR group are alive (86.7%), and 12 patients survived more than 2 years (8.8%).
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PMID:Evaluation of photodynamic therapy in advanced gastrointestinal cancer. 1014 43

4 patients with recurrent gynecological malignancy were treated photodynamically, 4 d after sensitisation with intravenous meso-tetra(hydroxyphenyl)-chlorin (m-THPC) at a dose of 0.15 mg/kg bodyweight (total dose ranged from 12-15 mg). Light at 652 nm was derived from a KTP-Dye laser (Diasonic) and delivered superficially at a total light dose of 20 J/cm2 (power density of 100 mW/sec). Within 24 h necrosis occurred which was restricted to the tumor area. There was serious bleeding occurred in 1 patient. All tumors responded to PDT, however woundhealing was significantly delayed and survival times were disappointingly short.
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PMID:Photodynamic therapy for recurrent gynecologic malignancy: a report on 4 cases. 1032 40


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