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)

Purpurins are modified chlorins with photodynamic properties. Their strong absorption in the red region of the visible spectrum makes them candidates for use in photodynamic cancer therapy. A series of metal derivatives of the free base purpurins have been synthesized and shown to cause tumor necrosis in transplantable tumors when exposed to visible light. In the following set of experiments, the effects of two metallo-derivatives (tin and zinc) of two purpurins, octaethylpurpurin (NT2) and etiopurpurin (ET2), and light on the N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide transplantable tumors in Fischer CDF(F344)/CrlBr rats were studied. The photodynamic activity was assessed by a short term assay using tumor dry weight 12 days after purpurin-PDT as a criterion of response. From these experiments it appears that SnET2 greater than SnNT2 greater than ZnET2 greater than ZnNT2 in photodynamic activity. SnET2 was further characterized by attempting to determine the time interval after systemic injection at which maximum therapeutic effect occurred. These studies shown that 24 h after metallopurpurin injection was the optimum time for treatment of tumors with visible light. In a final set of experiments, the effect of solar light on the skin of hairless mice injected with SnET2 was found to be much less injurious than with hematoporphyrin derivative.
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PMID:Metallopurpurins and light: effect on transplantable rat bladder tumors and murine skin. 214 8

A comparison of time-dependent localization patterns between lower, asymmetrical (AIPCS2a) and higher, symmetrical (AIPCS4) sulfonates of aluminum phthalocyanines in human malignant melanoma LOX transplanted to athymic nude mice from 1 to 120 hr after i.v. administration was made by means of laser scanning fluorescence microscopy. The lipophilic AIPCS2a was distributed mainly in tumor cells, while the hydrophilic AIPCS4 localized only in the vascular stroma of the tumor tissue. Concomitantly, comparative observations on the killing mechanism of photodynamic effects after treatment with a much lower i.v. dose of AIPCS2a and AIPCS4 plus laser light on the human tumor LOX were also made by morphological studies. Light and electron microscopy showed that there was a direct, extensive, photo-damaging action on all organelles and nuclear structure in the tumor cells after PDT with AIPCS2a; whereas the photo-induced injury to the tumor tissue after treatment with AIPCS4 and light was largely the consequence of initial functional vasogenic response and ultimate damage to vascular structure. These findings correlate well with the different localization patterns of the 2 dyes observed in human tumor tissues.
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PMID:Aluminum phthalocyanines with asymmetrical lower sulfonation and with symmetrical higher sulfonation: a comparison of localizing and photosensitizing mechanism in human tumor LOX xenografts. 221 Aug 87

The relationship between levels of in vivo accumulated photosensitizer (Photofrin II), photodynamic cell inactivation upon in vitro or in vivo illumination, and changing tumor oxygenation was studied in the radiation-induced fibrosarcoma (RIF) mouse tumor model. In vivo porphyrin uptake by tumor cells was assessed by using 14C-labeled photosensitizer, and found to be linear with injected photosensitizer dose over a range of 10 to 100 mg/kg. Cellular photosensitivity upon exposure in vitro to 630 nm light also varied linearly with in vivo accumulated photosensitizer levels in the range of 25 to 100 mg/kg injected Photofrin II, but was reduced at 10 mg/kg. Insignificant increases in direct photodynamic cell inactivation were observed following in vivo light exposure (135 J/cm2, 630 nm) with increasing cellular porphyrin levels. These data were inconsistent with expected results based on in vitro studies. Assessment of vascular occlusion and hypoxic cell fractions following photodynamic tumor treatment showed the development of significant tumor hypoxia, particularly at 50 and 100 mg/kg of Photofrin II, following very brief light exposures (1 min, 4.5 J/cm2). The mean hyupoxic cell fractions of 25 to 30% in these tumors corresponded closely with the surviving cell fractions found after tumor treatment in vivo, indicating that these hypoxic cells had been protected from PDT damage. Inoculation of tumor cells, isolated from tumors after porphyrin exposure, into porphyrin-free hosts, followed by in vivo external light treatment, resulted in tumor control in the absence of vascular tumor bed effects at high photosensitizer doses only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen limitation of direct tumor cell kill during photodynamic treatment of a murine tumor model. 252 60

Cell survival was investigated in an intraocular retinoblastoma-like tumour 30 min to 48 h after photodynamic therapy. The survival of the cells was assessed by an in vivo to in vitro colony forming assay, estimated by either the plating efficiency of the treated tumour cells compared to non-treated cells or the number of clonogenic cells per mg excised tumour. Curves showing cell survival as a function of the time between light irradiation and excision of the intraocular tumours were biphasic. This suggests more than one PDT tissue destruction mechanism in vivo (i.e. an early direct cell damage plus a subsequent late damage occurring in the tumour tissue left in situ after treatment). The delayed mechanism may be due to changes in the environment of the tumours probably caused by vascular damage. Tumour cells sensitised by Photofrin II in vivo and excised from the eyes were damaged by light when irradiated in vitro and this was dependent on the light energy dose. This showed that cellular Photofrin II uptake in the eye tumours was sufficient for direct cell damage and thus supports the suggestion that direct and indirect tumour destruction occurs in this eye tumour after photodynamic therapy.
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PMID:Photodynamic therapy effect in an intraocular retinoblastoma-like tumour assessed by an in vivo to in vitro colony forming assay. 252 1

Photochemotherapy (PDT) is based on the interaction of a phototoxic drug (HPD) retained by cancer tissues and excited with a specific laser light. We present here a phase I clinical trial including 54 patients selected on the grounds of non-operability and T1 NO MO staging (UICC) and divided into 3 groups: I) 24 squamous cell carcinoma (SCC), II) 14 adenocarcinomas (ADN) of the upper GI tract, III) 16 ADN of the rectosigmoid colon. All received an HPD infusion of 2.5 to 5 mg/kg I.V. 72 hours before being laser irradiated endoscopically (632 nm, 150 to 220 j/cm2). Results documented on histology obtained after grip biopsies and on resected specimens (6 cases), were classified as complete response (ST), partial response (PR) or no change (NC). Eleven patients of group I, 5 of group II, and 8 of group III (24/54 patients) were classified ST with a mean follow-up of 15.2 months. Analysis of resected specimens showed a complete disappearance of tumor tissue and prominent fibrosis all around the treated area. Adverse effects were noted in 22% of patients, PDT of rectosigmoid ADN gave a survival (life table analysis) at least equal to SCC. These results should allow clinical indications for PDT to be broadened in combined protocols.
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PMID:[Palliative treatment by photochemotherapy of 54 digestive cancers: phase I clinical trial]. 268 64

The purpose of this study was to investigate whether excitation of porphyrin could be related to nonlinear mechanisms of absorption of porphyrin itself or of the medium in which porphyrin is embedded. This possibility was proposed as an explanation for results of previous experiments where a Nd:YAG laser was used. An MS-2 sarcoma transplanted into the hind pad of BALB/c mice was used as the experimental tumor model. Mice were given HpD i.v. (25 mg/kg) 24 h before exposure to light delivered from an IR laser (1,060 nm). Since at dose-rates ranging between 600 and 1,200 mW/cm2 the thermal effect tended to mask the nonlinear effect, the temperature of the limb of mice was kept cold by running water. Irradiation performed under cooling conditions did not show any tumor growth inhibition. Experiments in vitro performed on HT-29 cells by a continuous wave (CW) or pulsed (Q-switch) Nd:YAG laser indicated no appreciable difference in DNA synthesis between irradiated and nonirradiated cells. Our results did not evidence nonlinear mechanisms of absorption by HpD with Nd:YAG laser both in CW and pulsed (nanosecond range) modes. Whether this effect should occur, in any case it is unlikely to be suitable to induce a photodynamic effect due to its low efficiency. Nd:YAG laser could induce a heating related effect, which can improve the therapeutic efficacy of PDT.
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PMID:A study on the possible involvement of nonlinear mechanism of light absorption by HpD with Nd:YAG laser. 294 43

While results concerning photodynamic treatments of cancers in pneumology or dermatology have been published regularly, few works have been devoted to gastroenterology. Twenty-seven non-operable patients bearing various G.I. tumors of less than 40 mm dia. have been treated by PDT for palliative purpose to appreciate the local efficacy of a single treatment. Before July, 1985, the parameters of treatment were 2.5 mg/kg of HPD injected intravenously for theoretical power of delivered laser light (630 mm) 300 mW. After July, 1985, HPD was injected at the dose of 5 mg/kg and the laser dose was 400 mW. A normalization of grip biopsies was observed on 12 patients (6 squamous cell carcinomas, 6 adenocarcinomas), transient in 3 cases. Our main finding is that PDT seems able to destroy significant volumes of tumor by itself although subsequent biopsies proved negative in very few cases. This method remains to be compared to others less sophisticated than the YAG laser.
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PMID:Photochemotherapy mediated by hematoporphyrin derivative in gastroenterology. 295 85

PDT represents another modality for the treatment of human malignancy. Photoactivated hematoporphyrins have definite antitumor activity in both in vitro and in vivo experimental systems. Much of the early clinical work involved treatment of patients with advanced, recurrent disease who had not responded to conventional therapy. Because good responses with acceptable toxicity have been obtained in these patients, active investigation continued and is aimed at defining the most appropriate sites and applications for the technique. Because of the limited depth of light penetration in tissue, the most promising sites may be those where there is limited thickness of tumor, such as in superficial skin lesions or carcinomas in situ involving the aerodigestive tract, bronchial tree, or genitourinary tract. Other potential uses include those where PDT could be combined with surgical or chemotherapeutic debulking, such as pleural mesothelioma or advanced stage ovarian cancer. Whether PDT can be of benefit in surgical cases where the margins of resection are close is an interesting but speculative notion at the present time. Clinical trials with hematoporphyrin derivative PDT in the sites mentioned are in progress. Laboratory work to better understand HpD also continues, as well as investigations into alternative photosensitizers with improved tumor localization, less cutaneous photosensitivity, and absorption peaks at deeper penetrating wavelengths of light. Attempts at measuring singlet oxygen, if successful, will permit the development of more meaningful dosimetry in order to correlate response with actual tissue levels of the purported cytotoxic agent. Hopefully, these and other developments in the field of PDT will improve the treatment for patients with cancer.
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PMID:Photodynamic therapy of cancer. 296 98

Using rats with tumor transplanted into the subcutaneous tissue, tumor resections done with either an ordinary scalpel or a laser scalpel were compared from the viewpoints of tumor recurrence and survival time. It was found that tumor resection using the laser scalpel and laser irradiation of the field after tumor resection were effective in preventing recurrence. With this concept in mind, 286 operations involving laser surgery were performed, including 179 for malignant tumor, most of which were cancers of the liver, esophagus, stomach and colon. Laser surgery for hepatoma and other malignant tumors yielded better results than ordinary surgery. Another experimental study of PDT (photodynamic therapy) for malignant tumor of the parenchymal organs was carried out. The uptake of HpD (hematoporphyrin derivatives) by the liver was as much as 1.5 times that by the digestive tract. The concentration of HpD in the tumor tissue of WKA rats with DAB hepatic tumor was twice that in liver tissue. However, the difference in HpD concentration between the tumor tissue and liver tissue is not large enough for PDT and this point requires further study.
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PMID:[The efficacy and limitations of laser surgery in malignant tumors]. 359 91

PDT of rat bladder cancer, induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) was studied. All animals were divided at random into three groups. Group 2 and 3 were treated by hematoporphyrin derivative (HPD)-laser PDT while group 1, without treatment, served as control. The results showed that the malignant lesions could be selectively and obviously destroyed, if the whole tumor area were sufficiently exposed to the laser irradiation. However, the normal bladder epithelium and muscle layer showed no histologic change. Similar reactions were found in papilloma of bladder which was considered as precancerous lesion. Thus, PDT may be beneficial to cancer prevention. Its role in prevention and treatment of bladder cancer should be further studied experimentally and clinically.
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PMID:[Photodynamic therapy (PDT) of bladder cancer in the rat]. 374 45


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