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Background: This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC)., Methods: Clinical studies on recurrent OSCC treated with PDT alone were included. Combined treatment strategies were excluded. The search was performed on Medline/Pubmed, Cochrane Library, Embase, Web of Science and ClinicalTrials.gov, manual search, and grey literature., Results: The eleven included studies were observational. The risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Quality Assessment Scale. The studies reported the use of hematoporphyrin derivative, Photofrin Ⓡ , Foscan Ⓡ and 5-aminolevulinic acid. Data on treatment response and survival was collected. Secondarily, postoperative courses and patient's quality of life/acceptance were reported whenever available. Photofrin Ⓡ and Foscan Ⓡ were the most used photosensitisers, with more complete responses. Lesions responding less favourably were on posterior regions or deep-seated in the tissue., Conclusions: Although treatment response differs between treatment protocols, PDT stands as a viable treatment option to be considered, as it can achieve therapeutic results and disease-free, long-lasting periods. Partial treatment responses may be of interest when achieving eligibility for other treatment strategies. Despite this study's limitations, which considered four photosensitisers, Photofrin Ⓡ was the most used but more recent photosensitisers like Foscan Ⓡ have greater chemical stability, tissue penetration, and may be more efficacious on recurrent OSCC., Competing Interests: Declaration of competing interest None, (Copyright © 2024. Published by Elsevier B.V.)

Background: Photodynamic therapy (PDT) is receiving increasing attention in treating non-small cell lung cancer (NSCLC) worldwide, but in clinical practice, the relationship between treatment effect and PDT light dose in NSCLC remains unclear. Therefore, we aimed to determine the optimal light dose for PDT by exploring molecular biomarkers and evaluating tumor growth data., Methods: We applied bioinformatics to identify promising genes and pathways in NSCLC and PDT. Then, the human lung adenocarcinoma cell line A549-bearing BALB/c nude mice were treated with hematoporphyrin derivative (HPD, 3 mg/kg) that is currently used widely for lung cancer treatment in the world even with photosensitization issues. After 48 h, tumor-bearing mice were irradiated superficially at doses of 100, 200, 300, 400, and 500 J/cm 2 . The tumor growth data and apoptotic molecules were assessed and calculated., Results: Bioinformatics results indicated that the apoptosis pathway was significantly enriched and caspase 3 was the most promising biomarker on prognosis in NSCLC-PDT. Compared to the untreated group, there was no difference in the relative tumor volume (RTV) of the 100 J/cm 2 group, while the RTV of the other treatment groups (200-500 J/cm 2 ) was significantly lower. In the 100 J/cm 2 group, there were significant differences in the complete remission (CR, 0 %) and the percentage of tumor growth inhibition rate (TGI%) over 75 % (20 %) compared with the other treatment groups, especially the 300 and 400 J/cm 2 groups (CR 70 %; TGI% 90 %). In the 300 and 400 J/cm 2 groups, the expression of caspase 3, cleaved-caspase 3, PARP1, and Bax was increased significantly, while Bcl-2 expression was significantly lower., Conclusions: Moderate doses of PDT (300 or 400 J/cm 2 ) are more effective than low (100 or 200 J/cm 2 ) or high doses (500 J/cm 2 ) in the A549 tumor-bearing mice model. Since the A549 tumor is more akin to human tumors in pathological behavior, these experimental data may contribute to improving HPD-PDT illumination protocols for favorable clinical outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

To investigate the effect and mechanism of 630-nm laser on human lung adenocarcinoma cell xenograft model in nude mice mediated by hematoporphyrin derivatives (HPD) and provide theoretical basis for clinical photodynamic therapy (PDT). Human lung adenocarcinoma cell xenograft model in nude mice was established and randomly divided into four groups: control group, pure photosensitizer group, pure irradiation group, and photodynamic treatment group. The tumor volume growth was compared, and the tumor growth inhibition rate was calculated. HE staining was used for routine pathological observation of tumor sections, and gross conditions of cells, interstitium, and blood vessels in several groups of tumor tissues were observed. TUNEL staining was used to observe and compare the apoptosis induced by photodynamic therapy. Real-time fluorescence quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression level of angiogenesis-related factors VEGF, HIF-1α and apoptosis-related factors Bax and Bcl-2 mRNA in the transplanted tumor tissues. Western blot was employed to detect the expression of angiogenesis-related proteins VEGF, HIF-1α and apoptosis-related proteins Bax, Caspase-3, and Bcl-2. Compared with the other three groups, the tumor growth inhibition rate of the photodynamic treatment group was significantly increased and the difference was statistically significant (P < 0.05). HE staining showed that the animal model of lung adenocarcinoma A549 was successfully established. TUNEL staining revealed that more apoptotic cells were found in the photodynamic treatment group, and the apoptosis index was calculated. Compared with the other three groups, the difference was statistically significant (P < 0.05). RT-PCR results showed that compared with the other three groups, the mRNA expressions of VEGF, HIF-1α, and Bcl-2 in the photodynamic treatment group decreased, while the expression of Bax mRNA increased(P < 0.05), and the differences were statistically significant. Western blot results showed that protein expressions of VEGF, HIF-1α, and Bcl-2 decreased in the photodynamic treatment group, while protein expression level of Bax and Caspase-3 increased (P < 0.05), indicating statistically significant differences. The 630-nm laser mediated by hematoporphyrin derivatives can significantly inhibit the growth of human lung adenocarcinoma xenograft tumor in nude mice, the mechanism of which is related to the inhibition of tumor angiogenesis by down-regulating VEGF and HIF-1α gene expression, and the promotion of tumor apoptosis by up-regulating Bax, Caspase-3, and down-regulating Bcl-2 gene expression.

Purpose: Although photodynamic therapy (PDT) has been shown to be effective in cancer treatment, its side effects, such as a long-lasting skin photosensitivity after the application, still cause patient's inconvenience. In this retrospective cohort study, our objective was to explore a more efficient but less phototoxic PDT for skin cancers., Methods: The PDT combined with a topical photosensitizer 5-aminolevulinic acid (ALA) and an intravenously injected light-sensitive agent hematoporphyrin derivative (HPD) was used to treat 26 patients with 41 skin cancer lesions in head and face. The findings were then compared with the results of the HPD-PDT alone and the ALA-PDT following CO2 laser ablation on 28 and 41 skin cancer patients, respectively., Results: The complete remission rate for the combined PDT was 100 % in 2 months and 97.6 % in a 6 months to 6 years trial after the treatment compared with those of 92.9 and 95.1 % for the HPD-PDT and the ALA-PDT after a single treatment, respectively. Moreover, while the patient treated with the HPD-PDT needs to avoid strong light exposure for 4-5 weeks, the combined PDT significantly reduced the period to 10-14 days. Also, in the combined PDT, the dose of the HPD, a pro-toxic light-sensitive drug, was much lower than that in the HPD-PDT., Conclusions: The combined PDT not only shows high cure rate for skin cancers but also decreases the dose of the pro-toxic HPD and significantly shortens the photosensitive period, from which the patients are able to benefit.

Introduction: What is the current status of photodynamic therapy (PDT) with regard to treating malignant brain tumors? Despite several decades of effort, PDT has yet to achieve standard of care., Purpose: The questions we wish to answer are: where are we clinically with PDT, why is it not standard of care, and what is being done in clinical trials to get us there., Method: Rather than a meta-analysis or comprehensive review, our review focuses on who the major research groups are, what their approaches to the problem are, and how their results compare to standard of care. Secondary questions include what the effective depth of light penetration is, and how deep can we expect to kill tumor cells., Current Results: A measurable degree of necrosis is seen to a depth of about 5mm. Cavitary PDT with hematoporphyrin derivative (HpD) results are encouraging, but need an adequate Phase III trial. Talaporfin with cavitary light application appears promising, although only a small case series has been reported. Foscan for fluorescence guided resection (FGR) plus intraoperative cavitary PDT results were improved over controls, but are poor compared to other groups. 5-Aminolevulinic acid-FGR plus postop cavitary HpD PDT show improvement over controls, but the comparison to standard of care is still poor., Conclusion: Continued research in PDT will determine whether the advances shown will mitigate morbidity and mortality, but certainly the potential for this modality to revolutionize the treatment of brain tumors remains. The various uses for PDT in clinical practice should be pursued., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Objective: The photodynamic therapy is a well-known method of treatment of both malignant tumors and non-tumor lesions in human patients. In the present study, we aimed at evaluating the in vitro efficacy of the new photosensitizing agents, vacataporphyrin (VP), and divacataporphyrin (DVP)., Materials and Methods: The effectiveness of VP and DVP was compared to well-known photosensitizers, that is, hematoporphyrin derivative (HPD) and chlorin e6 (Ce6) in identical in vitro conditions. The experiment was performed on a well-established breast cancer cell line, MCF-7 and compared to HCV 29T11-2-D1 cell line. Cells were incubated in standard conditions and they were exposed to different concentrations of VP, DVP, HPD, and Ce6, that is, 180, 90, 45, 22.5, and 10 µg/ml. After incubation with photosensitizers, the cells were washed, medium was exchanged and the cells were subjected to irradiation at the proper wavelengths, light intensity (100 mW/sq cm), and total light doses 4.5 and 9 J/sq cm., Results: Our results showed that the VP and DVP are potent photosensitizers and the photocytotoxic effect after the incubation with DVP was much better than that of VP. The cytotoxic effects of VP and DVP were less intensive than these of HPD and Ce6. VP and DVP also accumulated well in the tumor cells. Our results also indicated that the VP and DVP effectiveness on MCF-7 cells was photosensitizer dose and light dose dependent., Conclusion: The overall properties revealed by both new porphyrins and particularly a possibility for excitation at a higher wavelength and thus a deeper tissue penetration, make them promising candidates for further in vivo experiments., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: To investigate the mechanism of photodynamic therapy (PDT) in nude mice bearing human esophageal cancer cell line Eca-109 xenografts., Methods: A nude mouse model bearing human esophageal carcinoma was established by subcutaneous transplantation of Eca-109 cells. The mice were then randomized into 4 groups, namely hematoporphyrin derivative (HpD)-PDT group (given HpD and laser irradiation), exclusive laser irradiation group, exclusive HpD group and blank control group. In HpD-PDT group, the mice were exposed to irradiation at the light energy density of 120 Jsol;cm(2) delivered via a DIOMED 630 PDT system 24 h after intraperitoneal HpD injection, and the mice in exclusive laser irradiation group received only laser irradiation. Three days later, all the nude mice were sacrificed for determination of malondialdehyde (MDA) production, immunohistochemistry for caspase-3 protein and HE staining of the tumor tissue., Results: The MDA level was significantly higher in HpD-PDT group than in the other 3 groups (P<0.01), and comparable between the latter 3 groups. Expression of caspase-3 protein was similar between HpD-PDT group and the blank control group (P>0.05). Under light microscope, HE staining visualized massive tissue necrosis in HpD-PDT group with homogeneous red staining., Conclusion: In human esophageal carcinoma xenografts in nude mice, HpD-PDT generates singlet oxygen to result in direct tumor cell damage and cause MDA production. Caspase-3 may not be activated in the apoptotic pathway, suggesting that this pathway may not be caspase-3-dependent.

Hematoporphyrin derivative (HPD), a sensitizer used in photodynamic therapy (PDT) of malignancies, is progressively destroyed during the treatment. Prior studies suggested that upon PDT the photobleaching of HPD in tumor tissues is largely mediated by self-sensitized singlet oxygen. However, little is known about the role of other reactive oxygen species (ROS). The main aim of this work was to clarify the significance of H2O2, superoxide (O2.(-)) and hydroxyl (OH.) radicals in bleaching of HPD in tumor cells subjected to PDT. Experiments were performed on Ehrlich ascites carcinoma (EAC) cells, which were loaded with HPD in PBS and then irradiated with red light at 630 nm in the same buffer. Studies showed that photosensitization of EAC cells by HPD led to the formation of significant amounts of H2O2, O2.(-) and OH., and that these ROS could be involved in the photobleaching of HPD during PDT. In fact, we found that addition of catalase (CAT, a scavenger H2O2), Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and Tiron (scavengers of O2.(-)), Na-benzoate, mannitol and deferoxamine (scavengers of OH.) caused a substantial decrease in the rate of HPD photobleaching in EAC cells. In these cells, the inhibitory effects of Na-benzoate, mannitol and deferoxamine on the photodegradation of HPD correlated well with suppression of the OH. generation, a highly active oxidizer. In EAC cells, the glutathione redox cycle and CAT (scavengers of H2O2) as well as Cu/Zn-SOD was found to suppress the photoinduced degradation of HPD. It was also established that HPD can directly scavenge H2O2 and oxygen free radicals; in a phosphate buffer its second-order rate constants were measured as 5.51+/-0.32 x 10(3)M(-1)s(-1) (for the reaction with O2.(-)), 5.08+/-0.31 x 10(4)M(-1)s(-1) (for H2O2), and 3.44+/-0.08 x 10(10)M(-1)s(-1) (for OH.). Thus, our data suggest that OH. could be one of the main oxidants mediating the photobleaching behavior of HPD in malignancies. Studies showed that photoexcited moieties of HPD can oxidize cell proteins with the formation of protein peroxides (PPO), which currently are regarded as a new form of ROS. Model experiments suggest that PPO could also participate in bleaching of HPD in tumors treated with PDT. It was found that HPD may destroy in tumor cells after cessation of photoirradiation and that this event is largely mediated by the presence of H2O2, a precursor of OH(.).

Purpose: The role of photodynamic therapy (PDT) in the treatment of small cancers has been established in several clinical studies. Here, we report on the efficacy of PDT for early inoperable or recurrent non-small-cell lung cancer (NSCLC)., Methods and Materials: From June 1989 to November 2004, 40 patients with 50 NSCLC were treated with PDT. Twelve cases were inoperable for medical reasons and were staged as T1N0M0, and 28 had recurrent in situ carcinoma. Patients with residual disease after PDT received definitive radiotherapy and/or brachytherapy. Follow-up ranged from 6 to 167 months (median 43.59). Twenty of the 40 patients received i.v. injections of hematoporphyrin derivative (5 mg/kg), the other 20 had injections of porfimer sodium (Photofrin, 2 mg/kg). An argon dye laser (630 nm wavelength, 200-300 J/cm2) was used for light irradiation in 24 of the 40 patients, a diode laser (Diomed, 630 nm wavelength, 100-200 J/cm2) in the other 16., Results: PDT obtained a 72% complete response (CR) rate (36/50 treated lesions), that is 27 CR among the 37 Tis carcinomas and 9 among the 13 T1 cases. Kaplan-Meier curves showed a mean overall survival (OS) of 75.59 months (median 91.4 months). Two- and 5-year OS rates were 72.78% and 59.55%. The mean and median survival rates for patients with Tis stage were 86.5 and 120.4 months, respectively (standard error 9.50) and for patients with T1 disease they were 45.78 and 35.71 months, respectively; the difference was statistically significant (P = 0.03). No severe early or late PDT-related adverse events were recorded., Conclusions: PDT is effective in early primary or recurrent NSCLC, resulting in a CR rate of 72%. The incorporation of PDT in standard clinical practice, in combination with radiotherapy, warrants further investigation., ((c) 2007 Wiley-Liss, Inc.)

Background: Complete fading of port wine stains (PWS) is difficult to achieve with current laser treatments. Photodynamic therapy (Gu's PDT) could offer a very efficient alternative for PWS therapy., Patients and Method: 1949 lesions in 1385 patients were treated by PDT. Each patient received an intravenous injection of hematoporphyrin derivative (HpD) or hematoporphyrin monomethyl ether (HMME) at 3-7 mg/kg. Laser irradiation was performed on a 2 to 8 cm spot size. Different wavelengths (488.0 nm to 578.2 nm) were evaluated with a power density of 50-100 mW/cm2. Fluences ranged from 90 to 540 J/cm2., Results: Among the 1942 lesions, PWS clearance was observed in 99.7% of cases. Excellent results were achieved in 128 lesions (6.6%) (100% clearance), 746 lesions (38.3%) yielded to good results (clearance > 75%), 923 lesions (47.4%) showed moderate results (clearance 50-75%), 145 lesions (7.4%) showed poor results (clearance<50%) and in 7 lesions (0.3%) no visible change was observed. The pink port wine stains revealed better response to Gu's PDT with only one session. Conversely, purple stains in adult patients required 2 sessions or more., Conclusion: This new PDT technique is effective and highly selective, with almost no risk of scarring.

The aim of this study was to clarify the mechanism of the stimulatory effect of heat stress on generation of superoxide radical (O2-*) in tumors subjected to photodynamic therapy (PDT) with hematoporphyrin derivative (HPD). For this purpose, the effect of heating on the activity of xanthine oxidase (XOD) in tumor cells upon their photosensitization with HPD was examined; this enzyme is participated in purine catabolism and has the ability to generate O2-*, a precursor of H2O2 and very cytotoxic hydroxyl radical. The study was carried out on Ehrlich ascites carcinoma (EAC) cells, which were loaded with HPD in a serum-free medium and then irradiated with red light (lambda max = 630 nm) at 3 different temperatures (30, 37 and 44 degrees C). In the cells, the activity of XOD was assayed fluorometrically, using pterine as the substrate, whereas the production of O2-* by the nitro blue tetrazolium method. It was found that increasing of the temperature from 30 to 44 degrees C strongly (by approximately 2.5-fold) enhanced the generation of O2-* in EAC cells that correlated well with an increase in the rate of their photosensitized killing. Experiments showed that the intensification of O2-* formation could be mediated by the stimulatory effects of heating on the activity of XOD; namely, the 12 min treatment of EAC cells by HPD-PDT at a control (30 degrees C) temperature caused an about 2-fold growth in the activity of XOD, whereas the same light exposure at 44 degrees C led already to a 2.7-fold increase in the activity of this enzyme. However, incubation of EAC cells in the dark even at a hyperthermic (44 degrees C) temperature had no effect on their XOD activity. Thus, our findings strongly suggest that upon PDT with HPD the mild hyperthermia (approximately 44 degrees C) produced by photoirradiation might enhance the PDT-induced oxidative stress and, as a result, its tumoricidal effect via a rise in the activity of XOD. Besides, the obtained results suggest that severe hyperthermia (> 45 degrees C) could induce, contrary to mild hyperthermia, a reduction in the efficiency of HPD-PDT; we found that in EAC cells the raising temperature of an environment from 30 to 44 degrees C induced more than 2-fold increase in the activity of XOD, whereas further heating from 44 to 60 degrees C led to inactivation of this enzyme.

As a disease characterized by a polymorphic and fluctuant nature in its evolution, superficial transitional cell carcinoma of the bladder remains a perpetual therapeutic challenge. This raises a great interest in the development of new diagnostic and therapeutic photodynamic applications. This article describes recent facts in the field of bladder cancer photodiagnosis and gives a survey on ongoing research in photodynamic therapy. Fluorescence cystoscopy induced by different aminolevulinic acid compounds (e.g., ALA-HAL) is well accepted in the urological community as a user-friendly new diagnostic tool in the endoscopic management of bladder tumors and CIS. Photodynamic therapy based on the same photosensitizing agents remains experimental, but recent results raise hopes of new therapeutic directions.

Background and Objectives: We aimed to treat different pathologic types of basal cell carcinomas (BCCs) using photodynamic therapy (PDT)., Study Design/materials and Methods: Thirty lesions in six patients underwent PDT. The photosensitizer used was Photoheme, a hematoporphyrin derivative IX. It was injected intravenously at the dose of 2-3.25 mg/kg. After 24 hours, the lesions were illuminated by laser light (lambda = 632 nm, light exposure dose = 100-200 J/cm2). Lesions were evaluated pre and post-operatively and at follow-up sessions (of up to 6 months)., Results: After a single session of PDT, the average response rate in different histopathologic kinds of basal cell carcinoma (e.g., ulcerative, superficial, nodular, and pigmented forms) were 100%, 62%, 90%, and 14%, respectively. In patients who responded completely, the cosmetic results were excellent and there were no recurrence at 6th month of follow-up., Conclusion: Although PDT seems to be an effective treatment modality for superficial, ulcerative, and nodular BCCs, it is not recommended for pigmented lesions., (Copyright 2005 Wiley-Liss, Inc.)

Aim: To elucidate the mechanism of the potentiating influence of heating associated with photoirradiation on the antitumor efficiency of photodynamic therapy (PDT) with hematoporphyrin derivative (HPD)., Methods: The study was carried out on Ehrlich ascites carcinoma (EAC) cells, which were loaded with HPD in a serum-free medium and then irradiated with red light (lambda max=630 nm) at various temperatures. Cytotoxicity was estimated by the trypan blue exclusion assay., Results: Our data support the view that in PDT the hyperthermia (around 44 degrees C) produced by irradiation can enhance synergistically the HPD-photoinduced tumor eradication; it was found that raising the irradiation temperature from 30 to 44 degrees C caused a substantial (approximately 1.5 fold) increase in the rate of HPD-photosensitized inactivation of EAC cells, while hyperthermia (44 degrees C) itself showed little toxic effects towards the cells., Conclusion: Studies indicated that the potentiating effect of heating on the antitumor efficiency of HPD-PDT could be largely explained by the stimulation of reactive oxygen species formation such as H2O2, superoxide and hydroxyl radicals. It was also found that photosensitization of EAC cells by HPD caused a strong fall in the activity of catalase (CAT) and glutathione (GSH) peroxidase, and that heating sensitized the H2O2-detoxifying enzymes to HPD-photoinduced inactivation. Under HPD-PDT, these events could result in loss of protection against accumulating H2O2; we revealed that cell-bound CAT and the GSH redox cycle play an important role in the protection of EAC cells against HPD-PDT. Moreover, our findings suggest that during PDT with HPD, an increase in the temperature of tumors could enhance the efficiency of this therapy via the stimulation of a chlorin-type photoproduct formation.

Background: Laser photocoagulation of papillary hemangioma in von Hippel-Lindau disease often causes visual loss. Therefore, we applied photodynamic therapy for one patient., Case: A 36-year-old male had 3.2 x 2.6 mm capillary hemangioma of the optic disc associated with a fibrovascular membrane and exudative retinal detachment involving the whole macular area in his left eye. His visual acuity was 0.08., Treatment: Two days after the intravenous injection of 2 mg/kg of hematoporphyrin derivatives, the eye was irradiated with a dye laser of 630 nm wavelength, with irradiance of 637 mW/cm2 and a radiant exposure of 150-250 J/cm2. The exudative retinal detachment and hemorrhage in the tumor increased from day 1, but the tumor and exudative changes began to resolve after 3 weeks. The fibrovascular membrane was removed by vitrectomy. Three years after the treatment, the tumor was completely resolved, but the patient's visual acuity was 0.1 due to atrophy of the optic nerve and pigment epithelium of the macula., Conclusion: Although further investigation on optimal radiance avoiding damage to the optic nerve is still needed, photodynamic therapy is a promising therapeutic option for papillary hemangioma.

Objective: In this study, we investigated the efficacy of Super Lizer (SL) as a new light source in photodynamic therapy (PDT) with hyperthermia in an in vivo osteosarcoma tumor model., Materials and Methods: Nude mice in three study groups (PDT only, PDT with hyperthermia in low energy, and PDT with hyperthermia in high energy) and three control groups (no treatment, photosensitizer only, and hyperthermia only) were implanted subcutaneously with human osteosarcoma cells and injected with a photosensitizing hematoporphyrin derivative (HPD) at a total dose of 10 mg/kg, in all study groups and in control group 2. At 72 h after light treatment, mice were sacrificed., Results: The tumor volume growth rates in the heat-only (1.50) and PDT-only (1.40) groups were significantly lower than the growth rate in the no-treatment group (1.82). Further, the tumor volume growth rate in the PDT with hyperthermia in high-energy group (1.19) was significantly lower than in the heat- or PDT-only groups., Conclusion: Although non-laser PDT, including SL-PDT, may be beneficial only in the treatment of superficial tumors because of limited light penetration, PDT combined with hyperthermia may extend the utility of PDT in antitumor treatment. The use of SL as a new light source in PDT may significantly advance antitumor therapy due to its simplicity, ease, and cost benefit.

Photodynamic therapy (PDT) is a "drug and device" therapy that combines the use of a photosensitizing agent and a photosensitizer (a drug that selectively accumulates and is preferentially retained in dysplastic or neoplastic cells). When activated by light of a specific wavelength in the presence of oxygen, the photoactive compound produces rapid cell death in the target tissue. While studied in nearly every area of medicine, PDT has been applied most extensively in the treatment of Barrett's mucosa, dysplasia, and early and advanced cancer of the esophagus. This article represents an extensive survey of literature to review the experience gained with PDT and to assess its clinical value in the management of esophageal diseases.

This study addresses whether photodynamic therapy (PDT) is a valid therapeutic option in lung cancer treatment. A total of 24 articles were reviewed in two categories: advanced (G1) and early (G2) disease. Details considered included the following: 1) number of patients in each series; 2) staging; 3) methodology; 4) mortality; 5) morbidity; 6) survival; 7) relief of symptoms; and 8) concomitant treatments. G1 (636 patients) had severe endobronchial obstructive cancer and PDT was primarily for symptom relief. G2 (517 patients) had early stage cancer and were treated with PDT for curative intent. There was no procedure-related mortality in either group. G1 had a 5-28% incidence of skin sensitivity. Haemoptysis occurred in two series; one fatal, an incidence of 2.2%. Almost all patients had symptomatic relief. Patients with lower disease stage and better performance status had improved survival rates. G2 had a 8-28% incidence of sunburn. Three patients in one series (38 patients) had haemoptysis. Survival after 5 yrs in complete remission/response patients was 70%. This review suggests that bronchoscopic photodynamic therapy has indications in selected lung cancer patients with early or advanced stage disease. However, in the absence of a formal comparative study, no claim can be made of its superiority over other endobronchial therapies.

While photodynamic therapy is applied on neoplasm, photosensitisers tend to accumulate in neoplastic tissues. With appropriate wavelength light, it causes photochemical reaction and destructs neoplastic tissues. Its better selection for tumor tissue with effective photochemical reaction, and lower side effect make it widespread application in gynecologic oncology. At present, photodynamic therapy has been used in diagnosing and treating lower genital tract carcinoma in situ, and advanced malignant tumor such as vulval and ovarian carcinoma.

Background & Aims: Although esophagectomy is the standard of care for treating early adenocarcinoma in Barrett's esophagus, the procedure is associated with significant morbidity and mortality. For these patients, the multimodal approach of endoscopic mucosal resection and photodynamic therapy (EMR/PDT) may be a viable, less invasive option., Methods: A retrospective review (1996-2001) of all patients undergoing either combined EMR/PDT group or esophagectomy (SURG) for early-stage Barrett's adenocarcinoma was performed. Data were collected on patient demographics, tumor staging, procedure-related morbidity and mortality, persistence or recurrence of cancer, and cancer-related deaths after therapy. Differences in outcomes between the 2 groups were assessed., Results: Twenty-four patients were identified in the EMR/PDT group and 64 in the SURG group. The SURG group was found to have a significantly higher procedure-related complication rate compared with the EMR/PDT group (31 vs. 4; P < 0.01). There were no procedure-related deaths in the EMR/PDT group, whereas one death occurred in the SURG group as a result of complications. Eighty-three percent of patients (20 of 24) in the EMR/PDT group and all patients in the SURG group remained free of cancer over a follow-up of 12 +/- 2 and 19 +/- 3 months, respectively. Four patients in the EMR/PDT group failed to respond to therapy; 2 of them underwent alternate therapies and are free of disease, whereas the other 2 died of unrelated causes., Conclusions: The combination of EMR/PDT seems to be a viable and less morbid alternative to standard esophagectomy in patients presenting with early Barrett's esophageal adenocarcinoma. A prospective randomized, controlled trial of EMR/PDT compared with esophagectomy for managing early adenocarcinoma in Barrett's esophagus may be warranted.

Photodynamic therapy (PDT) is based on the concept that light irradiation can change an inert substance into an active one. In urology, hematoporphyrin derivative (HpD) and Photofrin (Axcan Scandipharm Inc., Birmingham, AL) are used most commonly as photosensitizing agents predominantly for the treatment of transitional cell carcinoma of the bladder. To investigate the basics for PDT of prostate cancer, several studies were performed on the optical characteristics of prostate tissue and prostate carcinoma tissue in vitro and in vivo and on the penetration depths of different laser wavelengths. Initial experimental studies to treat prostate cancer with PDT using HpD were done on Dunning tumors in rats. Combined with interstitial applicators, photodynamic therapy seems to have a great potential in the treatment of prostate carcinoma. However, it is an experimental treatment and even a preliminary evaluation will be possible only after the conclusion of clinical studies with the corresponding long-term results.

In the present study we have checked whether photodynamic therapy (PDT) may influence concentration of basic Fibroblast Growth Factor (bFGF) in in vivo conditions. We have implanted malignant tumor, i.e. BFS1 fibrosarcoma into BALB/c mice and have them treated using well established photosensitizer, hematoporphyrin derivative and new compound, hydroxygallium (III) phthalocyanine tetrasulfonic acid tetrasodium salt, BON-6. The administration of those compounds was followed by light irradiation using a halogen lamp at proper wavelengths. Our results indicate that in vivo photodynamic therapy may cause a significant decrease in bFGF concentration and this phenomenon is accompanied by prolongation of survival of treated animals.

The spectral properties of new photosensitizer ZnPcS2P2, PsD-007 and HMME, as well as traditional photosensitizer HpD have been studied by comparing their spectra in physiological saline and in physiological saline with 10 percent serum. Experimental results show that the maximum absorption peaks for PsD-007, HMME and HpD in the physiological saline with 10 percent serum appear at 400 nm in the soret region, while at 670 nm for ZnPcS2P2. The fluorescence excitation spectra closely resemble the absorption spectra. When excited by the light at the wavelengths of 413 and 514.5 nm, the fluorescence emission peaks for PsD-007, HMME and HpD appear at 625 and 690 nm, respectively. The fluorescent excitation efficiency of the same photosensitizer with the same concentration excited by the light at the wavelength of 413 nm is about three fold higher than that at 514.5 nm. Furthermore, the fluorescent excitation efficiency is the highest for HMME, but is lower for HpD and lowest for PsD-007. These results are significant in the selection of photosensitizers for photodynamic diagnosis and therapy.

Background: At present there is no ideal minimally invasive method for ablating inflamed synovium in joints that has been unresponsive to optimal medical management in patients with rheumatoid arthritis. The aim of this study was to determine whether photo-dynamic therapy could be used for this purpose., Methods: In a rabbit knee model of rheumatoid arthritis the pharmacokinetics of the photosensitizer Haematoporphyrin Derivative (HpD) into periarticular tissues and blood was measured following intravenous injection of HpD. The second phase of the study was to determine the histological effect of HpD activation by 63 nm light delivered via an intra-articular optic fibre using a dye pumped KTP-YAG laser. The light dose was varied from 0-200 joule/cm2., Results: Pharmacokinetic studies determined that inflamed synovium rapidly accumulated HpD, with peak levels being reached 12 h following intravenous injection. The ratio of HpD uptake into inflamed synovium versus peri-articular quadriceps muscle was found to be 22.8. Histological examination of the treated knees indicated that selective destruction of inflamed synovium was achieved at light doses 100 joules/cm2 and above. No significant effect was observed on normal intra-articular tissues., Conclusion: We have demonstrated that the first generation photosensitizer HpD selectively accumulates within inflamed -synovium. Activation of HpD by intra-articular light administration resulted in selective ablation of the inflamed synovium. These findings indicate that PDT offers potential as a new selective, minimally invasive synovectomy technique.

Background: Hematoporphyrin derivatives (HpD) as sensitizers for photodynamic therapy (PDT) in advanced esophageal cancer carry the risk of prolonged photosensitivity of the skin. New sensitizers such as 5-aminolaevulinic acid (ALA) with low rates of skin phototoxicity appear to be promising alternatives. The aim of this study was to evaluate the efficacy of ALA compared with HpD for PDT in advanced esophageal carcinoma regarding phototoxicity of the skin, reduction of dysphagia, tumor stenosis and length, and Karnovsky performance status., Methods: After diagnostic workup, photosensitization was done in 22 patients with ALA (60 mg/kg body weight, oral, 6 to 8 hours before PDT) and in 27 patients with a hematoporphyrin derivative (2 mg/kg body weight, intravenously, 48 hours before PDT). The light dose was calculated as 300 J/cm fiber tip. Light at 630 nm was applied using a pumped dye laser. In both groups, additional hyperbaric oxygenation was applied at a level of 2 absolute atmospheric pressure., Results: Improvement regarding dysphagia, stenosis diameter, and tumor length could be obtained in both treatment arms with a significant difference in favor of the HpD group (p = 0.02; p = 0.0000; and p = 0.000014, respectively). A questionnaire of patients in the HpD group confirmed that the ability of swallowing a meal was superior compared with the discomfort from limitation to sun exposure. No sunburn or other major treatment-related complication occurred in both treatment arms., Conclusions: Despite the limitations of a nonrandomized study, photosensitzation with HpD seems to be more effective in PDT of advanced esophageal carcinoma compared with ALA.

Numerous studies have shown that lysosomal proteinases play an important role in carcinogenesis. The enzymatic activity of tumor-associated proteases is counter-balanced by specific inhibitors. Photodynamic therapy (PDT) is a technique which involves photoexcitation of sensitizing drugs retained in neoplastic tissue that is subsequently destroyed. Intraperitoneal injections of hematoporphyrin derivative (HpD) were given at a dose of 20 mg/kg in rats transplanted with mammary carcinoma. A halogen lamp was used 24 hours later at 630 +/- 20 nm and total dose--200 J/sq.cm. Cysteine proteinase inhibitor (CPI) was dissolved in saline and injected subcutaneously in doses of 50 mg and 200 mg per animal. The effectiveness of the treatment was evaluated with regard to survival time and tumor response and to depth of necrosis. In several cases tumors completely disappeared following HpD-PDT + CPI. The number of complete tumor responses was higher when PDT + 200 mg of CPI was used, i.e. 6 out of 10 rats. Promising results have also been obtained with regard to survival time of treated animals and to induction of tumor necrosis. We may presume that a combination of PDT and proteinase inhibitors could be a useful tool in further anticancer studies and, hopefully, in anticancer therapy.

Purpose: The role of apoptosis related proteins in the response of human malignancies to photodynamic therapy (PDT) is under investigation. The aim of the study was to examine the role of p53 and of bcl-2 protein expression in the response to PDT., Materials and Methods: Paraffin-embedded material from 37 patients with early esophageal cancer treated with PDT (argon dye laser after intravenous injection of hematoporphyrine derivative) was studied immunohistochemically for p53 protein nuclear accumulation and bcl-2 cytoplasmic expression. Patients with residual disease after two rounds of PDT received definitive radiotherapy. In a subsequent in vitro study, W138 human lung fibroblasts and W138-SV-40 virus transformed were assessed for their sensitivity to PDT. The constitutive bcl-2 overexpression of the transformed cells vs. normal cells (assessed with RT-PCR) was 16-fold., Results: Positive bcl-2 and p53 expression was noted in 10 out of 36 (27%) and 14 out of 36 (39%) patients, respectively. Seven out of 11 tumors (63%) with bcl-2 expression responded completely to PDT vs. 6 out of 26 (23%) of cases with no bcl-2 expression (p = 0.02). No association of p53, T-stage and of histology grade with response to PDT or PDT/RT was noted. The sensitivity to PDT of transformed human fibroblasts compared to normal ones was 4 times more at a fluence of 4.3 J/cm2 (4% vs. 1% cell kill) as well as at a fluence of 5.4 J/cm2 (8% vs. 2% cell kill)., Conclusion: Bcl-2 protein expression is associated with favorable response to PDT and can be used as a predictor of cancer response to PDT. This finding can be explained by experimental studies showing that PDT induces selective degradation of the bcl-2 protein, leading to apoptosis by decreasing the bcl-2/bax ratio. Studies on PDT combination with agents targeting bcl-2 (i.e. taxanes) are on going to eventually assess a super-additive effect.

Photodynamic therapy seems to be able to control high-grade dysplasia within Barrett's esophagus about 80% of the time. Long-term results are not available, but the treatment is promising. Given the success with surgical intervention, however, use of photodynamic therapy should be reserved for nonsurgical candidates at the current time. The complications that occur with photodynamic therapy are not trivial and must be weighed against the potential benefits.

Purpose: Photodynamic therapy (PDT) has shown remarkable activity in a variety of human cancers. In the present study, we report the effects of PDT on inoperable early-stage esophageal cancer., Methods and Materials: Sixty-two patients were treated with an argon dye laser (630 nm wavelength, 300-800 mW of power, energy dose of 200-300 J/cm) after intravenous injection of 5 mg/kg of hematoporphyrin derivative. Eighteen patients (29.5%) had in situ carcinoma (Tis), 30 (48.5%) had T1-stage cancer, 7 (11%) had T2-stage cancer, and 7 (11%) had recurrent disease in the anastomotic area after previous surgery without evidence of invasion outside the lumen. Patients with residual disease after two rounds of PDT received definitive radiotherapy. Patients were evaluated for response to therapy and survival. The follow-up time ranged from 3 to 90 months (median, 32 months)., Results: The complete response (CR) rate was 37% (23 of 62) in patients who received PDT alone and 82% (51 of 62) in those who also received radiotherapy. The CR rate after PDT alone was statistically higher (p = 0.04) for patients who had Tis/T1 lesions (21 of 48; 44%) than for those with T2-stage disease (2 of 7; 28%) or recurrent tumors (0 of 7; 0%). Fifty-two percent of patients who had CR following PDT alone did not suffer local tumor recurrence. The median local progression-free survival times after PDT and additional radiotherapy (in cases with incomplete response) was 49 months for Tis- and T1-stage lesions, 30 months for those with T2-stage disease, and 14 months for patients with locally recurrent disease. Patients who completely responded to PDT had a median overall survival (OS) of 50 months, which was significantly longer (p < 0.003) than that of patients not responding to PDT. Toxicity was minimal; we recorded three cases of esophageal stenosis (7%) and one case of tracheo-esophageal fistula (2.5%) after combined PDT and radiotherapy., Conclusion: PDT is an effective regimen for early esophageal cancer, giving a CR rate of about 40%, long-term local control and favorable overall survival. Additional radiotherapy in cases of incomplete response to PDT is effective and potentially curative in another 45% of cases.

Aim: Differential radiomodification induced by 2-deoxy-D-glucose (2-DG) is proving to be a feasible modality for optimizing tumor radiotherapy. Our earlier work on Ehrlich ascites tumor cells has shown that pretreatment with hematoporphyrin derivatives increases the uptake and phosphorylation of 2-DG. Moreover, the alteration induced in bioenergetic profile was more drastic and less reversible. The promising combination of hematoporphyrin derivatives and 2-DG has been further evaluated in the Ehrlich ascites tumor bearing mice for determining the effects on radiotherapeutic response., Materials and Methods: Solid tumors (average volume = 0.9 +/- 0.1 cm3) implanted in Swiss-albino strain "A" mice were focally irradiated (10 Gy) using 60Co teletherapy. Drugs were administered intravenously. Tumor bioenergetics was assessed by 31P MR spectroscopy., Results: The uptake and phosphorylation of 2-DG was observed to be increased following pretreatment with hematoporphyrin derivatives. Upon hematoporphyrin derivatives + 2-DG treatment followed by irradiation, the intracellular pH reduced and a remarkable increase in glycerophosphorylcholine and inorganic phosphate levels was observed., Conclusion: The present study demonstrates the potential of hematoporphyrin derivative pretreatment in increasing the bioavailability of 2-DG in a mice Ehrlich ascites tumor model. The finding may have interesting clinical implications in the form of increased manifestation of the radiation-induced damage in the case of use of these drugs as a potential adjuvant in radiotherapy of tumors.

Background and Study Aims: Patients with cancers of the head and neck have a strong tendency to develop early synchronous and metachronous carcinomas of the esophagus. In many of these patients, whose general condition is poor as a result of alcohol and tobacco abuse, the second primary cancers require minimally invasive treatment. The aims of this study were to evaluate the efficacy of photodynamic therapy for the treatment of early esophageal carcinomas and to compare the results obtained with three different photosensitizers (hematoporphyrin derivative), porfimer sodium (Photofrin II), and meta-(tetrahydroxyphenyl)chlorin (m-THPC)., Patients and Methods: Thirty-one early squamous cell carcinomas (Tis or T1a) of the esophagus were treated by photodynamic therapy in 24 patients. Nine tumors were treated with hematoporphyrin derivative, eight with Photofrin II and 14 with m-THPC., Results: The early cancers were cured in 84% of patients after a mean follow-up period of 2 years. Because the number of cases included in each group was small, the differences in recurrence rates for the different photosensitizers could not be evaluated statistically, but m-THPC was more phototoxic, induced a shorter period of photosensitization of the skin, and had better selectivity than either of the other photosensitizers. There were four major complications: two stenoses and two esophagotracheal fistulas., Conclusions: Photodynamic therapy eradicates early squamous cell carcinomas (Tis and T1a) of the esophagus efficiently. Transmural necroses leading to fistulas can be avoided by using a low-penetrating wavelength of laser light (green light at 514.5 m instead of red light at 630 or 652 nm). Stenoses always result from circumferential irradiation of the esophageal wall, and this can be avoided by using a 180 degrees or 240 degrees windowed cylindrical light distributor.

Objective: To obtain an objective assessment of the curative effectiveness of photodynamic therapy (PDT) for port wine stain (PWS), we investigate the relationship between the microvascular perfusion changes of PWS and the blanching of the lesions before and after PDT., Methods: Twenty-four patients (18 females and 6 males with a total of 28 lesions) suffering from PWS were treated with PDT. The lesions of various extents were located on the face and neck. After intravenous injection of photosensitizer hepatoporphyrin derivative (HpD), the copper vapor laser was adopted as light source and the lesions of PWS were irradiated. The laser Doppler perfusion imager (LDI) was used to measure the microcirculatory perfusion of PWS before and after PDT and comparison with the normal skin was done., Results: All the lesions showed remarkable decrease of tissue perfusion after PDT. It was shown that the mean, maximal and minimal values of tissue perfusion in the pre-treatment group were significantly higher than those in control group (P < 0.01). Six months after PDT, the mean, maximal and minimal values of perfusion with the lesions were reduced, with significant difference from pre-treatment group (P < 0.01), but no significant difference from control's. The colors of lesions were correlated with decrease of microcirculatory perfusion, which became lightened close to normal skin color without causing any scarring., Conclusions: PDT is one of the most effective modalities for PWS. The microcirculation perfusion can reflect the degrees of PWS objectively. The curative effectiveness of PDT for PWS is due to tissue microcirculation response.

Background: Despite their relatively localized nature, the therapy for surgically unresectable cholangiocarcinomas has been largely unsuccessful. Photodynamic therapy is a promising technique for both curative and palliative treatment of this malignancy. The effectiveness of a potential new photosensitizer, mono-l-aspartyl chlorin e6 (NPe6), was compared with that of a traditional drug, hematoporphyrin derivative (HpD), in photodynamic therapy administered to a human cholangiocarcinoma model., Methods: An established cholangiocarcinoma cell line was inoculated subcutaneously in the left back of male nude mice age 8 weeks. After a predetermined tumor size was reached, the mice were randomly assigned to either a control group or an experimental group. Experimental tumor-bearing mice received either HpD (5 mg/kg or 10 mg/kg) or NPe6 (2 mg/kg, 5 mg/kg, or 8 mg/kg) followed by photoradiation. HpD and NPe6 were administered intraperitoneally at 24 and 2 hours, respectively, prior to light exposure. Photoradiation was conducted using a xenon-mercury arc lamp with a 405-650 nm filter at a light flux of 80 J/cm2. Tumor response was assessed by serial tumor volume measurements., Results: Control mice showed an estimated mean tumor volume doubling rate of 9.0 days. Triaxial tumor measurements correlated well with autopsy measurements (correlation coefficient = 0.9). Overall differences in tumor volume reduction were detected (P < 0.001) among the three groups: HpD, NPe6, and controls (photoradiation only, HpD only, or NPe6 only). The degree of tumor volume reduction was superior for dosages of NPe6 compared with all dosages of HpD (P < 0.05). Although a dose effect was detected (P < 0.05) for HpD and separately for NPe6, a consistent dose-response relationship was not observed for either. Inhibition of tumor regrowth was better for NPe6 compared with HpD. The depth of tissue injury was significantly increased (P < 0.05), by 67%, for 5-8 mg/kg of NPe6 compared with 5-10 mg/kg of HpD. The duration of cutaneous photosensitization was also decreased for NPe6 compared with HpD., Conclusion: Photodynamic therapy with HpD or NPe6 was effective inducing tumor regression in the cholangiocarcinoma model in this study. At the dosages studied, NPe6 appeared to induce greater tumor regression than HpD, with decreased tumor regrowth and duration of cutaneous photosensitization.

Intravesical therapy has been used in the management of superficial transitional cell carcinoma (TCC) of the urinary bladder (i.e., Ta, Tl, and carcinoma in situ) with specific objectives which include treating existing/residual tumor, preventing recurrence of tumor, preventing disease progression, and prolonging survival. The initial clinical stage and grade remain the main determinant factors in survival irrespective of the treatment. Presently, bacillus Calmette-Guerin (BCG) immunotherapy remains the most effective treatment and prophylaxis for TCC (Ta, Tl, CIS) and has positive outcomes on tumor recurrence rate, disease progression, and prolongation of survival. Prostatic urethral mucosal involvement with bladder cancer can be effectively treated with BCG intravesical immunotherapy-it has demonstrated a reduction in tumor recurrence rates, but has had no positive impact on disease progression or prolongation of survival. Interferons, keyhole-limpet hemocyanin (KLH), bropirimine, and PHOTOFRIN-photodynamic therapy (PDT) are under investigation in the management of TCC and early results are encouraging. This comprehensive review highlights recent developments in intravesical therapy of bladder cancer and summarizes the mechanisms of action of BCG, and the important role of intravesical BCG immunotherapy and other immunotherapeutic agents in the therapy and prophylaxis of superficial TCC of the urinary bladder.

Photodynamic therapy (PDT), an experimental cancer therapy, was studied in an animal model of chemically-induced epithelial dysplasia and squamous cell carcinoma. PDT was performed 24 hours after i.v. injection of 2.5 mg/kg bw Photofrin, and using 100 J/cm2 incident light at two activation wavelengths (514.5 nm or 625 nm). Two days after PDT, the majority of rats macroscopically showed a marked erythema of the entire palatal region. Microscopically all the rats showed oedema, haemorrhage, and necrosis of the epithelium of the intermolar area. The long-term results were not so favourable. No evidence of disease was found in 6 out of 20 rats in the 514.5 nm group and in 2 out of 20 rats in the 625 nm treated group. Epithelial dysplasia was found in 14 out of 20 rats in the 514.5 nm group, and in 18 out of 20 rats of the 625 nm treated group. Squamous cell carcinomas were found in 4 out of 20 rats treated with 514.5 nm and in 7 out of 20 rats in the 625 nm treated groups. Comparing both treatment wavelengths, better results were obtained in the 514.5 nm groups as this wavelength gave less normal tissue damage. Based on the results of this study the application of PDT for the treatment of field cancerization and squamous cell carcinoma of the oral cavity, is discussed.

Background and Study Aims: Tumor ingrowth through self-expanding metal stents presents a difficult problem for management. The techniques for treating tumor ingrowth have not yet been well described, and the optimal endoscopic approach is not clear. We have recently used photodynamic therapy (PDT) to treat tumor ingrowth through uncovered nitinol mesh stents., Patients and Methods: Four patients (mean age 73) with obstructive adenocarcinomas of the distal esophagus had received self-expanding stents for palliation of their dysphagia. After stent placement, tumor ingrowth had caused progressive dysphagia in all of the patients; the dysphagia was graded on a scale from 0 (normal) to 4 (inability to swallow liquids). All of the patients received PDT treatment., Results: After PDT, excellent palliation of the dysphagia was seen in all of the patients, with a mean improvement in the dysphagia score of 2.25 and a mean dysphagia-free interval of 92 days. There were no major complications., Conclusion: The use of PDT to treat tumor ingrowth through self-expanding metal esophageal stents is effective and safe.

Purpose: Photodynamic therapy (PDT) involves the selective destruction of neoplastic cells through the activation of a photosensitizer by light. We have previously shown that the photosensitizer Photofrin (porfimer sodium) is selectively accumulated in transformed lesions destined to become malignant, but not yet definable histologically as precancers. The aim of this investigation was to determine if this premalignant tissue could be selectively destroyed by systemically administered Photofrin activated by 630 nm red light via an argon dye laser., Materials and Methods: The carcinogenic model used was the DMBA (9, 10 dimethyl 1,2 benzanthracene)-treated hamster cheek pouch. The animals were treated with 0.5% DMBA in acetone thrice weekly for 6 weeks (experiment I, premalignant lesions), or 12 weeks (experiment II, malignant lesions). Ten animals were in experiment I; nine animals were in experiment II. These were divided into experimental and control subgroups. The 6-week experimental group received PDT and CO2 laser incision into the DMBA-treated area. The CO2 laser was used as a promoter of neoplasia in a field that had already undergone initiation from the DMBA treatment. The control groups received either CO2 laser incision alone into the DMBA-treated field or CO2 laser incision and argon pumped dye laser treatment (without Photofrin). The 12-week experimental group received PDT after CO2 laser excision of tumors. The controls received CO2 excision alone, or CO2 excision combined with postoperative hyperthermia., Results: One hundred percent (three of three) of cheeks in experiment I receiving PDT developed necrosis of the treated area within 24 to 48 hours, but 0% (0 of three) subsequently developed tumors. No necrosis was seen in control cheeks receiving Photofrin without irradiation (0 of four) or irradiation without Photofrin (0 of six), and 56% (five of nine) of cheeks exposed to identical carcinogenic stimulus, without PDT, developed tumors (n = 9). In experiment II, 0% (0 of six) of cheeks receiving postoperative PDT developed tumor recurrence. In experiment II controls, 50% (three of six) of cheeks that underwent excision and hyperthermia developed tumor recurrence. In cheeks treated only with CO2 laser excision of tumors, a recurrence rate of 67% (four of six) was noted. These results were found to be statistically significant by the Student t-test on the binomial distribution (P < .01). One animal was treated with DMBA for 6 weeks, administered Photofrin, and the right cheek was irradiated and the animal was left for 30 weeks. The irradiated cheek epithelium necrosed but no cancer developed, whereas the positive control cheek developed a large cancer., Conclusion: These results suggest that photodynamic therapy possesses significant potential in elimination of premalignant tissue. This could be beneficial in treating potentially premalignant lesions such as oral leukoplakia, and useful as adjunctive therapy in removal of areas of field cancerization adjacent to surgical sites.

Photofrin is a potent sensitizer which localizes, among other sites in membranes of malignant cells. To evaluate the effect of photodymanic therapy (PDT) on specific antitumoral immunological response, we used a chromium release assay to compare the specific cytolytic activity (CLA) of primed mouse spleen T lymphocytes sensitized against syngeneic mastocytoma P511 cells. P511 cells or lymphocytes or both were treated or not with Photofrin and/or light (514 nm). Photofrin alone (1 microg/ml, 2 h) reduced CLA by 59% when P511 cells were treated although this decrease was not drug dose dependent. Photofrin (1 microg/ml, 2 h) followed by light (25 J/cm2) reduced CLA by 35% in a drug dose dependent manner. Longer incubation times led to reduced CLA inhibition (10% for 3 h incubation) after Photofrin followed by light. The light dose (25, 37, 50 J/cm2) did not influence CLA for a given Photofrin concentration. Photofrin alone (0.5 microg/ml, followed by light (25 J/cm2 for 2 h) reduced CLA respectively by 8 and 45% only when lymphocytes were treated. When lymphocytes and P511 cells were treated with Photofrin alone or followed by light (25 J/cm2), CLA was also reduced (by 19 and 41% respectively). This type of damage can be evaluated in terms of antigen expression on the target cells, on the lymphocyte T receptor, on H-2 (histocompatibility major complex), or on lymphocyte activity after PDT.

Two major steps in our study on the treatment of skin tumors by photochemotherapy (PCT) were the development of a skin tumor model in hairless mice by chemical carcinogenesis and by the use fluorescence spectroscopy, a semi-quantitative and non-invasive method, to determine the time after i.p. injection of photosensitizer when the tumor/normal skin ratio is the highest. Carcinogenesis provided mice bearing many benign papillomas and these were used to determine the tumor/normal skin ratios of two photosensitizers by fluorescence spectroscopy. Hematoporphyrin derivative (HpD) (5 mg/kg body weight) and m-tetra(hydroxyphenyl)-chlorin (m-THPC) (0.3 mg/kg body weight) were injected, and fluorescence measured at 4, 8, 24, 48, 72 and 96 h after injection. The tumor/normal skin ratio was 6.2 for HpD and 5.1 for m-THPC. The times required to reach these ratios were 48 h for HpD and 72 h for m-THPC. Published reports indicate that m-THPC gives a much higher tumor/normal skin ratio than HpD. These results must be confirmed by organic extraction. Photodynamic therapy with the same doses of HpD and m-THPC used in this pharmacokinetic study must also be carried out to compare the toxicities of the two photosensitizers and to determine which is best for this type of tumor.

Photodynamic therapy (PDT) has been investigated extensively, both experimentally and clinically, as an adjunctive treatment in the neuro-oncological field. It is based on the more selective accumulation of a photosensitizer in malignant than normal tissue with low systemic toxicity. Subsequent light activation induces photo-oxidation, followed by selective tumour destruction via vascular and direct cellular mechanisms. Malignant brain tumours carry a lethal prognosis with a median survival of 15 months despite surgery, radiotherapy and chemotherapy. PDT is therefore a logical therapeutic concept for brain tumours infiltrating into normal brain. In this review, all the available data on patients treated with haematoporphyrin derivative-mediated PDT are critically analysed. Over 310 patients have been reported in the literature suffering from primary or recurrent malignant brain tumours which were treated with PDT following tumour resection in open clinical phase I/II trials. This number includes 58 patients treated at our own institution. Variations in the treatment protocols make evaluation scientifically difficult; however, there is a clear trend of increased median survival after surgical resection and one single photodynamic treatment. PDT is generally well tolerated and side effects consist of moderate increased intracranial pressure and prolonged skin sensitivity to direct sunlight. The current available data indicate that PDT is a safe treatment, which is well tolerated by the patients and yields an improvement in survival of those with malignant brain tumours. Conclusive information can be expected from controlled clinical trials which are currently being designed. The results raise the hope that PDT will be a valuable addition to the armamentarium for the treatment of cerebral malignancies.

We have reviewed the results of clinical investigations into the use of photodynamic therapy (PDT) with intravenous injection of hematoporphyrin derivative (HpD), Photofrin (PF) and Sn-protoporphyrin (Sn-Pp) or oral administration of delta-aminolevulinic acid in the treatment of skin cancers and/or psoriasis. Bowen's disease was highly responsive, provided that adequate light and HpD or PF doses were delivered. In contrast, poor results were shown for squamous cell carcinoma, and the rates of complete response of basal cell carcinoma ranged between 0% and 100%. Treatment failures could be related to the delivery of low drug and/or light doses, but differences in the thickness and pigmentation of the treated lesions may play a relevant role. Good palliation was almost always achieved in patients affected by primary and secondary breast carcinomas, although complete eradication of tumors was very rare. PDT is a very promising treatment modality for both Mediterranean and HIV-related Kaposi's sarcoma, because it appears to be effective, can be repeated and is not associated with immunosuppressive activity or significant systemic toxicity. PDT of psoriasis with low doses of Sn-Pp, HpD or PF plus UVA light and PF plus 630 nm light proved to be effective and was associated with mild, dose-related and reversible photosensitivity.

The photodynamic therapy of cutaneous disease is developing more rapidly than that of other organs due to the accessibility of the skin to photosensitizers and light. The use of hematoporphyrin derivative, with its prolonged photosensitivity of normal skin, is gradually being replaced by a new generation of tetrapyrrolic photosensitizers. These are designed to absorb at longer wavelengths for deeper tissue penetration. Many also feature a greatly reduced photosensitizing potential of uninvolved skin. Another major development is the topical and systemic use of aminolevulinic acid for inducing the formation of endogenous porphyrins in cells which result in photosensitivity. This regimen is currently used quite extensively due to the easy availability of both drug and suitable light sources. However, continued investigation of the underlying mechanisms and their regulation will help to improve this specific photodynamic regimen. Currently, researchers use a whole array of therapeutic regimens and schedules for the evaluation of treatment efficacy. A certain uniformity of both treatment parameters and evaluation criteria will help to improve more rapidly our understanding of photodynamic sensitization in skin disease. This will also help us to define the right place and targeting strategies for photodynamic therapy in dermatology.

Photodynamic therapy (PDT) has been used clinically for the treatment of malignant brain gliomas. However, the efficacy of this treatment to date has remained equivocal. This study focused on determining the sensitivity of 9L glio sarcoma in Fischer 344 rats to PDT with increasing doses of 632 nm light and making a comparison of the responses of normal and tumor tissue in the brain at these doses. This sensitivity was then correlated with the concentrations of Photoforin present in these tissues at the time of treatment. Our study indicates that the level of Photofrin in the tumor was 13 times that present in normal brain 48 h after injection. However, this selective localization of the photosensitizer was not reflected in a selective tissue response to PDT. There was minimal tumor response to a dose of 35 J cm-2, which has been reported previously to cause necrosis to the normal brain. Increasing energy dose levels resulted in an increased tumor response to PDT; however, normal tissue remained more sensitive than tumor tissue at all energy dose levels examined. These data indicate that, although Photofrin is retained to a significantly higher degree in the tumor than in the normal brain tissue, the normal brain is more sensitive than the tumor to PDT under the conditions outlined in this study.

Photodynamic therapy (PDT) is an experimental cancer treatment modality. PDT is based on the accumulation of a photosensitive dye in premalignant and malignant lesions. A certain period of time after the dye has been administered, tumor tissue may contain more of the sensitizer then the surrounding normal tissues. When tissue containing the sensitizer is exposed to light of a proper wavelength and dose, a photochemical reaction between sensitizer and light will occur. The activated photosensitizer reacts with available oxygen which subsequently damages cells and eventually may cause necrosis of the tumor. Photosensitizers can also be used for fluorescence detection. If a tumor contains more of the photosensitizer than the surrounding normal tissue, its fluorescence can potentially be utilized to detect tumors. Analogous to PDT, this can therefore be referred to as photodynamic detection (PDD). This paper reviews the basic mechanisms and clinical applications of PDT and PDD. Emphasis is placed on PDD and PDT with the photosensitizer Photofrin for detection and treatment of premalignant epithelial lesions and squamous cell carcinomas of the oral mucosa.

The photocytotoxicity characteristics of aluminium phthalocyanine chloride (AIPc), aluminium phthalocyanine disulphonate (AlS2Pc), aluminium phthalocyanine tetrasulphonate (AlS4PC) and haematoporphyrin derivative (HpD) were compared using primary cultures of human meningioma cells. Cells were preincubated with the photosensitising agent for 16 h, then illuminated for 15 min with broad band red light (5 OW/cm2). The resultant cytotoxicity was assessed by tetrazolium (MTT) reduction 24 h later. AlPc was found to be 400, 10,000 and 250 times more potent that AlS2Pc, AlS4Pc and HpD, respectively, as an in vitro photosensitizing agent for meningioma cells. The subcellular localisation of AlPc, AlS2Pc, AlS4Pc and HpD in meningioma cells was determined by confocal laser scanning microscopy. None of the agents localized to the nucleus. The distribution of ALPc was quite diffuse through the cytoplasm. In contrast, AlS2Pc and AlS4Pc were localized vesicles suggestive of lysosomes, and HpD in membranous organelles distinct from mitochondria. AlPc and HpD were tested with five different meningioma samples and provided a range of IC50 values from 0.009 to 0.022 OM and from 3.5 to 6.5 OM, respectively. When the MTT assay with AlPc was performed 0, 24, 48 and 72 h after illumination, the mean IC50 values were 0.25, 0.037, 0.019 and 0.012 OM, respectively, indicating that the cytotoxic effect continued to increase up to 72 h. Cells were incubated with AlPc and HpD for different times up to 24 h before exposure to light. AlPc cytotoxicity was half-maximal with an incubation time of 8 h, whereas HpD cytotoxicity was half-maximal with an incubation time of 2 h, implying slower uptake kinetics for AlPc than for HpD. These data indicate unique features of AlPc which suggests its application as a potent, non-toxic photosensitizer in the photodynamic therapy of human meningiomas.