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Preclinical studies show improved prediction of treatment outcome using [ROS] rx than light fluence rate or PDT dose. We demonstrate ROSED in a clinical setting. Explicit dosimetry of light fluence, photosensitizer concentration, and oxygen concentration is used to quantify the reactive oxygen species explicit dosimetry (ROSED) during Photofrin-mediated pleural PDT. Light fluence and photosensitizer concentration were measured by a customized multi-channel PDT dose dosimeter system. Diffuse correlation spectroscopy (DCS) contact probes were sutured to the pleural cavity wall after surgical resection of pleural mesothelioma tumor to monitor tissue blood flow (BFI) during intraoperative PDT treatment. Tissue oxygen concentration can be determined by utilizing tumor blood flow measured by DCS. Large inter- and intra-patient heterogeneities in [ROS] rx were observed although an identical light dose of 60 J/cm2 was prescribed to all patients. This study summarizes the current results of ROSED for a Phase II pleural PDT clinical trial. [ABSTRACT FROM AUTHOR]

Multispectral singlet oxygen dosimetry (MSOLD) provides a mean for direct detection of singlet oxygen, responsible for tumor kill for type II PDT. An InGaAs spectrometer or an InGaAs detector coupled with to narrow beam filters (1200, 1240, 1250, 1270, 1300 nm) via 1 mm optical fibers are used to measure singlet oxygen (SO) luminescent spectrum in in-vitro and in-vivo conditions. The spectrum, after fitted to a phosphorescence background a gaussian function for the singlet oxygen peak, is used to determine the singlet oxygen (SO) emission signal. The MSOLD signal is then compared with the singlet oxygen explicit dosimetry (SOED) results, based on direct measurements of light fluence (rate), Photofrin concentration, and tissue oxygenation concentration. MSOLD signal is affected by tissue absorption and scattering and is increasing with increasing Photofrin concentration and light fluence rate. MSOLD is feasible in vitro and in vivo for detecting SO directly. [ABSTRACT FROM AUTHOR]

Background Iron oxide (Fe 3 O 4 ) nanoparticles (IO-NP) were recently employed in medical applications as a diagnostic tool and drug carrier. Photofrin (PF) is a photosensitizer that clinically is used in Photodynamic therapy (PDT). Study design The photosensitivity of PF and Rose Bengal (RB) mixed with (IO-NP) on red blood cells (RBCs) lysis was investigated. Second, Photohemolysis for post-irradiation (delayed) and during irradiation (continuous) with PF, RB and IO-NP combinations at different concentrations was investigated. Third, the photohemolysis rate, relative lysis steepness and power-concentration dependant parameter were evaluated by modeling and fitting the data using Gompertz function and power law. Methods RBCs were isolated from healthy male human volunteer. Washed cells (7.86 × 10 6 cells/mm 3 ) were incubated with PF only or with IO-NP for 45 min at 37 °C then irradiated to a range of temperatures (4–41 °C). CPH results were recorded and evaluated using Gompertz function. Results The relative steepness of the photohemolysis curves was approximately independent on light dose for delayed irradiation. The presence of IO-NP increases the rupturing time for 50% of the RBCs. Photohemolysis rate for delayed irradiation using the power law, led to 1.7 and 2.3 power dependence, respectively, for PF only and PF mixed with IO-NP. The power dependence of continuous irradiation measurements showed inverse proportionality for different concentrations of IO-NP combined with 2 μg/ml PF concentration and 1.5 μg/ml for RB concentration. Conclusion Photosensitization of RBC with PF or RB mixed with IO-NP inhibited rupturing erythrocyte membrane and therefore a consideration should be taken against their combination in clinical applications. [ABSTRACT FROM AUTHOR]

Objectives Photodynamic therapy (PDT) is a very effective treatment for superficial malignancies that does not result in loss of normal tissue. Here, we report successful PDT treatment of superficial oral cancers and its clinical outcome with long-term follow up. Materials and methods Thirty-four superficial oral squamous cell carcinomas were treated with PDT, and the effects were evaluated. Each patient received Photofrin (2 mg/kg) intravenously 48 h prior to light irradiation. Photoradiation was performed at doses of 100–150 J/cm 2 using a 630-nm wavelength excimer dye laser. Results Six months after PDT, 30 patients (88.2%) showed complete responses while 9 patients (26.5%) had local relapses during long-term follow-up. The 5-year overall survival, disease-specific survival, and disease-free survival rates were 76.5%, 84.6%, and 63.3%, respectively. Lesions with red patches had a significantly higher recurrence rate than lesions with white patches. Accurate evaluation of the extent of lesions and appropriate photoradiation were important in improving outcomes. Adverse events observed included sunburn and sequestrum formation of alveolar bone. No abnormal laboratory values or systemic complications were observed. Conclusion PDT using Photofrin as the photosensitizer is an effective treatment modality for superficial oral carcinomas, with excellent healing and minimal side effects. [ABSTRACT FROM AUTHOR]

• With screening, a large number of early stage and curable lung cancer has been diagnosed. • Surgery and Radiosurgery (SBRT) can be curative for these patients. • Photodynamic therapy (PDT) can also be curative for these patients but is underutilized. • PDT delivered by navigational bronchoscopy is an innovative means to treat these patients. • This case report shows how PDT can be curative for a nonsurgical and non radiosurgical patient. Photodynamic therapy (PDT) is an FDA approved treatment for lung cancer. In the United States the photosensitizer porfimer sodium (Photofrin®, Pinnacle Biologics) is intravenously introduced at 2mg/kg. After approximately 48 h, illumination to activate the photosensitizer is initiated, with 630nm red light at 200J/cm, delivered by fiber-optic catheter, brought to the tumor endo- bronchially, and delivered for 500 s. This will create, in the presence of oxygen, a Type II Photodynamic Reaction (PDR) which generates singlet oxygen species that are tumor ablative. Classically, PDT for lung cancer has been employed for symptomatic central and obstructing tumors with great success. This case report describes an innovative approach to treat a peripheral, early stage lung cancer employing magnetic navigation and endobronchial treatment. We report on a 79 year old male with numerous comorbidities including pulmonary fibrosis, who was found to have a biopsy proven peripheral and solitary non-small cell cancer. Due to prior SBRT (stereotactic body radiation therapy) with dose levels causing radiation fibrosis, he was not a candidate for repeat SBRT, and he was not a surgical candidate due to comorbidities. Tumor control with PDT was achieved without treatment related morbidity. This report details our findings. [ABSTRACT FROM AUTHOR]

• PDT is successful for lung cancer treatment. • PDT is generally used in central lesions. • This report features PDT for peripheral lung cancer. Photodynamic therapy (PDT) is an internationally approved ablation technique for endo-bronchial lung cancer. The majority of reported outcomes are for central and obstructing lesions where excellent long term control is possible. With the current trend of screening high risk for lung cancer populations, a larger cohort of patients are now diagnosed with earlier stage disease. When these early tumors are located in the lung periphery the current therapeutic options include surgery or radiation therapy. Still, many patients may not be candidates or amenable for these procedures. As PDT is a well tolerated non-thermal outpatient therapy to treat lung cancer and as newer bronchoscopy techniques allow for treatment of peripheral lesions, PDT may be an option. We report a case of a primary non-small cell lung cancer treated by interstitial PDT through placement of the diffusing fiber via magnetic navigational bronchoscopy. Forty eight hours post 2 mg/kg intravenous (IV) injection of Photofrin®, a single 500 second illumination of 200 J/cm at 630 nm was directed to the solitary peripheral lesion without complication. On day 30, as a part of planned therapy, lobectomy was undertaken. Pathology reported necrosis and no viable remaining tumor. At 90 days follow up, the patient remains well,with no evidence of disease. Additional details follow in the report. [ABSTRACT FROM AUTHOR]

• Microfluidic device performs single parallel test for different light irradiations. • Eight different intensities are generated from a single light-emitting diode. • Eight different color dye concentrations function as light intensity filters. • Optimum light intensities and photosensitizer doses were determined for cell lines. • High-throughput microfluidic system analyzes effects of light intensity during PDT. : Photodynamic therapy utilizes light energy with a photosensitizer (a light-sensitive drug) to kill cancer cells through creation of singlet oxygen via light activation. When a photosensitizer is injected into the bloodstream and exposed to a specific wavelength of light, it generates oxygen to destroy or damage nearby cancer cells, while minimizing side effects on normal cells. Although photodynamic therapy is effective for treating cancer, various parameters, such as the optimum light intensity and photosensitizer dose, are currently poorly understood due to the complexity of conventional experimental schemes. : To effectively perform a simultaneous single parallel test for several different light irradiation conditions on each cell, a microfluidic device was developed to generate eight different intensities from a single light-emitting diode source, through eight different color dye concentrations functioning as light intensity filters. To show that this novel high-throughput microfluidic system can analyze the effects of various light intensities during photodynamic therapy, the optimum light intensities and photosensitizer doses were determined for two different cancer cell lines. : Optimum light intensities and photosensitizer were determined for all cell lines. The photodynamic therapy effects in response to different irradiated light intensities were characterized by analyzing cell viability after photosensitizer treatment : The developed platform is capable of being used as a photodynamic therapy screening tool. The proposed platform provides a simple and robust way to optimize the combined parameters of light intensity and dosage for diverse types of cancer cells. [ABSTRACT FROM AUTHOR]

Summary: Objective: To investigate the effectiveness and side effects of photofrin-photodynamic therapy (PDT) for intractable bronchial lung cancer. Methods: Thirty patients were classified as stage II–IV intractable bronchial lung cancer with lumen obstruction after they failed previous treatment regimens such as surgery, radiotherapy and chemotherapy. PDT was performed with 630nm laser light (Diomed) delivered through cylinder diffusing tip quartz fibers that was passed through the biopsy channel of a flexible endoscope 48h after intravenous injection of the photosensitizer photofrin (2mg/kg body weight). 72h after the first irradiation, the endoscopic procedure was repeated, necrotic tissues were mechanically removed and the deep original lesions and newly exposed cancer lesions were re-treated, and, if necessary, the areas were cleaned repeatedly. Results: The total response rate CR+PR was 86.7%, and the mean percentage of obstruction due to tumors at different treated sites decreased from 90% to 16.7% at discharge after PDT. The KPS score was significantly improved after PDT. Conclusions: PDT of intractable bronchial lung cancer effectively reduces the amount of lumen obstruction, and improves the patient's quality of life. It may be an effective palliative treatment with minor side effects on patients with advanced bronchial lung cancer. [Copyright &y& Elsevier]

• The highest extrusion bond strength was shown by group 1 canal disinfected with Riboflavin and 17% EDTA at all three levels. • The lowest extrusion bond strength was displayed in group 5 canal cleaned with 2.25% NaOCl and 17% EDTA (control). • Intragroup assessment disclosed a decrease in EBS from cervical one-third to apical one-third in all experimental groups. To assess the influence of different photosensitizers activated by PDT as a disinfectant in comparison to conventional sodium hypochlorite (NaOCl) on the EBS (extrusion bond strength) of FRCP with radicular dentin. A total of fifty single-rooted human maxillary central incisors with fully developed apices were selected. Endodontic treatment of samples was performed using 10 K file to obtain patency than sequentially with a 25 K file followed by rotary pro tapers till F2 with constant irrigation. The canal was dried and obturated with corresponding gutta-percha and sealer. A Peso reamer was employed to prepare post space. Based on canal disinfection regimes, samples were divided into five groups. Group 1 Riboflavin (RF)+17%EDTA, group 2 Rose bengal (RB) +17%EDTA, group 3 Curcumin CP +17%EDTA, group 4 Porfimer sodium, Photofrin (PS) +17%EDTA and group 5 2.25% NaOCl +17% EDTA (control). Following disinfection, the canal space of all specimens was dried followed by FRCP cementation. Specimens were placed on a Universal testing machine (UTM) for EBS. The type of bond failure was evaluated using a stereomicroscope. ANOVA and Tukey multiple comparison tests were used to compare means. The highest EBS was shown by group 1 canal disinfected with riboflavin (RF) and 17% EDTA at all three levels. The lowest EBS was displayed in group 5 canal cleaned with 2.25% NaOCl and 17% EDTA. Intragroup assessment disclosed a decrease in EBS from cervical one-third to apical one-third in all experimental groups. Intergroup comparison revealed group 4 using PS and 17% EDTA and group 5 canal disinfected with 2.25% NaOCl and 17% EDTA at all three levels of root structure coronal, middle, and apical exhibited comparable EBS (p >0.05). Root canal dentin treated with different PS (RF, RB, CP) has the potential to be used as canal disinfection as it demonstrates better EBS than the conventional disinfecting regime (2.25% NaOCl +17% EDTA). PS and 17% EDTA as a canal disinfectant need further investigation. [ABSTRACT FROM AUTHOR]

Summary: Background and objective: Pancreatic cancer is a leading cause of cancer-related deaths in men and women. Early clinical studies suggest that photodynamic therapy (PDT) might be a useful modality in the management of this deadly disease. In this study, the photocytotoxicity of Photofrin-mediated PDT on different human pancreatic cancer cells (BxPc-3, HPAF-II, Mia PaCa-2, MPanc-96, PANC-1 and PL-45) was examined. Materials and methods: After co-incubating cancer cells with Photofrin (0–10μg/ml) for 4h, the cells were irradiated with 0–6J/cm2 of 630nm light. The effect of Photofrin PDT on the survival of cells were examined using tetrazolium-based colorimetric assay and clonogenic assay. PDT-induced apoptosis was analyzed by flow cytometry. Expressions of apoptosis-related proteins were determined by western blot analysis. Results: Photofrin PDT strongly inhibited the survival of pancreatic cancer cells. A small portion of cells (<15%) underwent apoptosis 24h after PDT at LD50. Cleavage of caspase-3, caspase-8, caspase-9 and PARP after PDT were also confirmed. BxPc-3, Mia PaCa-2, MPanc-96, and PANC-1 cells were more sensitive and HPAF-II and PL-45 cells less sensitive. Conclusion: Photofrin PDT can induce apoptosis and inhibit survival of human pancreatic cancer cells. [Copyright &y& Elsevier]

Summary: Background: Photodynamic therapy (PDT) is a minimally invasive treatment modality for early and superficial malignancy or premalignancy in the head and neck regions. However, few studies have examined the use of Photofrin-mediated PDT to manage early carcinoma and dysplasia in the oral cavity. Methods: Between January 2004 and November 2008, 25 T1 to T2 patients with N0 oral squamous cell carcinoma and mucosal dysplasia in the oral cavity were treated by Porfimer sodium (Photofrin®)-mediated PDT at Nagasaki University Hospital. Clinical responses were evaluated according to the guidelines of the Response Evaluation Criteria in Solid Tumors (RECIST). After the PDT and a 2-year follow-up period, disease specific survival rates were then calculated. Results: A total of 30 regions in 25 patients (18 with squamous cell carcinoma and 7 with epithelial dysplasia with hyperkeratosis in the oral cavity) were treated by PDT. Complete response was achieved in 24 of the 25 patients (96%), with a partial response found in the remaining patient. For the three patients who exhibited recurrence at 4, 5, and 15 months after PDT, salvage surgery or a second PDT was performed. Of these three patients, one died due to another disease, while one died due to local lymphatic metastasis that occurred during the follow-up period. Overall, the disease specific survival rate was 95.8%. Treatment-related edema and pain emerged within 24h after irradiation. Pain control using non-steroid anti-inflammatory drugs and opiates was required for 3–4 weeks in all patients. Complete healing was attained at 4–6 weeks after the treatment. No persistent problems related to functional or esthetic outcomes were noted. [Copyright &y& Elsevier]

Abstract: We aimed to investigate the role of the ABCG2 transporter in the efficacy of sonodynamic therapy (SDT) with Photofrin in the glioma stem-like cells (GSCs) isolated and cultured from U251 glioma cells. Immunocytochemistry and flow cytometry analyses showed that ABCG2 was overexpressed in GSCs, and the percentage of ABCG2-positive GSCs was approximately 100%. The effect of ABCG2 on Photofrin extrusion in the absence or presence of a specific inhibitor of ABCG2 (fumitremorgin C; FTC) was investigated by determining the intracellular concentration of Photofrin in GSCs incubated with 20μg/ml Photofrin. Extrusion of Photofrin by ABCG2 was inhibited by 10μM FTC, which significantly increased the intracellular Photofrin concentration (p <0.05) from 0.32±0.11μg/106 cells to 0.89±0.13μg/106 cells. MTT and TUNEL assays showed that the antitumor effect of SDT (incubation of GSCs with 20μg/ml Photofrin for 6h in the dark and ultrasonic activation at 1.0MHz and 0.5W/cm2 for 2min) was significantly improved by FTC pretreatment (p <0.05). Moreover, incubation of GSCs with FTC significantly increased the relative production of ROS in response to SDT. The overexpression of ABCG2 in GSCs results in efflux of Photofrin, indicating that the antitumor effect of SDT with Photofrin may be reduced in GSCs overexpressing ABCG2. However, since FTC improves the efficacy of SDT in GSCs by inhibiting ABCG2-mediated efflux of Photofrin, FTC may be useful in SDT treatment of ABCG2-expressing cancer cells. [Copyright &y& Elsevier]

Summary: Objective: To compare the short-term curative effect of photodynamic therapy (PDT), PDT combined with chemotherapy and chemotherapy alone on the advanced esophageal cancer patients. Methods: Retrospective analysis of 90 patients of esophageal cancer underwent PDT, PDT combined with chemotherapy and chemotherapy alone from 2004 to 2007 (stages III–IV), including 27 cases received PDT alone, 33 cases received PDT combined with chemotherapy and 30 cases chemotherapy alone. The enrolled patients were treated with intravenous administration of Photofrin as the photosensitizer at a dose of 2mg/kg. 630nm laser irradiation was performed through optical fiber that passed through the biopsy channel of a flexible endoscope after 48h. Two days later, the necrotic tissue was removed, and the primary sites and other newly identified lesions were subjected to a second irradiation and then the residual necrotic tissue was removed according to the patients’ condition. Electronic endoscopy was performed to observe the effectiveness on tumor after 1 month. In PDT combined with chemotherapy group, chemotherapy regimen was 5-FU and DDP, administered 4 cycles after PDT and chemotherapy alone group only chemotherapy regimen 5-FU and DDP for four cycles. All the 90 patients were followed up for 2 years. Results: Symptomatic palliation rate of the PDT alone group, the complex treatment group and chemotherapy alone group was 85.2%, 93.9% and 60.0%, respectively, and effective rate under endoscopy was 85.2%, 90.9% and 63.3%, respectively, there is no statistically significant difference; the survival rate of 2 years was 29.6%, 54.5% and 16.7%, respectively, and medium survival time is longer (III stages 13m, 22m, 10m; IV stages 7m, 5m, 4m), there is statistically significant difference (p =0.046). Conclusion: PDT combined with chemotherapy for the advanced esophageal cancer is superior to PDT alone and chemotherapy alone. [ABSTRACT FROM AUTHOR]

Summary: Photodiagnosis (PD) for cutaneous malignancy attempts to differentiate between normal and diseased skin without the need for histological evaluation. This technique exploits natural or induced differences in fluorescent signatures between these tissues. The technique may be as simple as using ultraviolet light in combination with clinical exam to as complex as optical tomography. While the need is great due to the enormous number of skin lesions currently requiring physical biopsy, the results so far generated are not as specific or sensitive as is required in the clinic. This brief review outlines the value of PD, its potential applications and shortcomings as well as a short primer on the most common technique employed in clinical practice. [Copyright &y& Elsevier]

Summary: Background: Photodynamic therapy (PDT) is being widely used for treatment of cancer and non-malignant diseases. The mechanisms of phototoxicity to solid tumor are not yet completely understood. Knowledge of the inherent sensitivity of endothelial cells in comparison to tumor cells would be helpful to predict tumor response to PDT, and thereby optimize treatment protocols. Methods and results: The intrinsic sensitivity of rodent endothelial and tumor cells to PDT was studied using an in vitro clonogenicity assay that strictly controlled for light and photosensitizer exposure, as well as cellular photosensitizer and oxygen concentration. Taking into consideration cell size, ploidy and glutathione content, no significant difference in sensitivity to phototoxicity was observed between tumor and endothelial cells. Electron microscopy studies were also conducted to examine endothelial and tumor cells for differential cellular damage following interstitial PDT of rat prostate tumor. No evidence for selective damage to endothelial cells was demonstrated. Conclusions: Rodent tumor cells and endothelial cells are equally susceptible to Photofrin-mediated PDT damage. Sufficient photosensitizer accumulated in solid tumor seems to be one of the key factors for PDT effectiveness. [Copyright &y& Elsevier]

Abstract: Photodynamic therapy (PDT) with a photosensitizer and laser irradiation has been shown to have potential effects in cancer chemotherapy. However, the commercial drug clinically gave many problems due to the poor solubility of the photosensitizer in water and the photosensitivity as an adverse reaction of PDT. We have examined best condition on the liposomalization of Zn-complexed coproporphyrin I (ZnCPI) as novel photosensitizer. The difference of pH in buffer significantly changed the ZnCPI entrapped ratio. The entrapped ratio of ZnCPI in PBS(−) buffer was 10.8±0.3%, whereas, these levels in some lactate buffer (below pH 5.0) increased. The change between the molecular form⇔ionic form of ZnCPI was occurred due to the change of the pH of buffer, and the amount of ZnCPI in the liposomal membrane changed. The difference of this level was considered to be contributed by the change of zeta potentials. Next, we examined the effect of the different pH of the buffer in liposomal preparation on the ZnCPI distribution in each tissue after each liposome administration. At 2 and 6h post-injection of ZnCPI liposome (pH 4.6), the ZnCPI concentration in the plasma of Ehrlich ascites carcinoma bearing mice was shown to be higher compared to that in other groups. The ZnCPI concentrations in the tumor after 2 and 6h of ZnCPI liposome (pH 4.6) treatment were shown to be higher than that in other groups. In conclusion, it is considered that the ZnCPI liposome (pH 4.6) had the effective antitumor activity with laser irradiation without the adverse reactions. [Copyright &y& Elsevier]

Summary: Objectives: To evaluate the clinical response and adverse effects of Photofrin photodynamic therapy (PDT) in patients with relapse nasal pharyngeal cancer. Methods: Thirty patients with relapse nasal pharyngeal cancer were randomly divided into PDT group and chemotherapy group. In PDT group, patients received intravenous administration of Photofrin (2mg/kg b.w.) and 48h later light (200–300J/cm) was delivered by a 630nm diode laser through a cylinder diffuser under endoscopic assistance. Two days after PDT the necrotic tissues were removed and newly identified sites were subject to another round of light irradiation. In chemotherapy group, the routine cisplatin and 5-fluorouracil (DDP/5-FU) remedy was used. Endoscopic and radiological examinations were performed during 6 months follow-up. The Karnofsy Score was used to evaluate the quality of life. Results: The local response and nasal cavity obstruction remission rate in PDT group were better than that in chemotherapy group. The Karnofsy Score was also improved in PDT group. Conclusion: This pilot study suggests that Photofrin PDT is effective and safe in treatment of advanced nasal pharyngeal cancer and management of nasal obstruction. [Copyright &y& Elsevier]

Abstract: In this report a low-cost illumination device for in vitro photodynamic treatment (PDT) is presented based on the use of light-emitting diodes mounted in an array-like arrangement. The diode array constructed in our laboratory is characterized in terms of irradiance as a function of the current applied, spatial homogeneity and effects of prolonged irradiation on media temperature. The efficiency for applications within in vitro PDT is demonstrated by analysis of the survival of the A431 human cancer cell line sensitized with either hypericin, meta-tetra (hydroxyphenyl) chlorin (mTHPC) or Photofrin and irradiated with appropriate diode types of the respective wavelength. According to the results obtained, a diode-based array for illumination represents an inexpensive technical alternative for stable, reproducible, homogeneous and specific irradiation for in vitro PDT experimentation. [Copyright &y& Elsevier]

Abstract: The invasive nature of malignant gliomas makes treatment by surgery alone extremely difficult. However, the preferential accumulation of photosensitisers in neoplastic tissues suggests photodynamic therapy (PDT) may be useful as an adjuvant therapy following tumour resection. In this study, the potential use of three different photosensitisers, namely Photofrin, 5-aminolevulinic acid (5-ALA) and calphostin C in the treatment of glioma was investigated. The uptake, cytotoxicity on U87 and GBM6840 glioma cell lines were determined by flow cytometry and MTT assay respectively. Their effect on glioma cell invasiveness was evaluated by (1) measuring the levels of matrix degradation enzymes matrix metalloproteinase (MMP)-2 and -9 using gelatin zymography, and (2) Matrigel invasion assay. The results showed that uptake of calphostin C reached saturation within 2h, while Photofrin and 5-ALA induced protoporphyrin IX (PpIX) levels elevated steadily up to 24h. Photocytotoxic effect on the two glioma cell lines was similar with LD50 at optimal uptake: 1μg/mL Photofrin at 1.5J/cm2; 1mM 5-ALA at 2J/cm2 and 100nM calphostin C at 2J/cm2. The inhibition in cell proliferation after Photofrin treatment was similar for both cell lines, which correlated to more cells being arrested in the G0/G1 phase of the cell cycle (P <0.01). By contrast, U87 was more sensitive to calphostin C whereas GBM6840 was more susceptible to 5-ALA treatment. The ability of both cell lines to migrate through the Matrigel artificial basement membrane was significantly reduced after PDT (P <0.001). This might be due to a decreased production in MMP-2 and MMP-9, together with the reduction of adhesion molecule expression. Photofrin was most superior in inhibiting cell invasion and calphostin C was least effective in reducing adhesion molecule expression. Taken together, PDT could be useful in the treatment of gliomas but the choice of photosensitisers must be taken into consideration. [Copyright &y& Elsevier]

Abstract: In recent years, photodynamic therapy (PDT) with a photosensitizer and laser has been given attention, especially for the treatment of superficial cancers, such as lung, gastric, bladder and cervical cancer. In this study, in order to enhance the efficacy of PDT, photofrin liposome (PF-Lip) was prepared with dimyristoylphosphatidylcholine, dimyristoylphosphatidylglycerol and cholesterol. Polyethyleneglycol modified photofrin liposome (PF-PEG-Lip) was prepared by modification of PF-Lip with monomethoxypolyethyleneglycol-2.3-dimyristoylglycerol. PF-Lip and PF-PEG-Lip entrapped with photofrin with 81.0±5.9 and 81.2±9.2%, respectively. The particle size of each liposome was 114.3±5.7nm (PF-Lip) and 118±3.5nm (PF-PEG-Lip), respectively. It was suggested that PEGylated liposomes has no effect on the trapping ratio of PF and particle size. Phototoxicity was enhanced by liposomalization, especially PEG-modification. However, PF-PEG-Lip inhibited the uptake of photofrin into tumor cells. The amount of singlet oxygen from photofrin solution (PF-sol) and each liposome was PF-PEG-Lip≒PF-Lip>PF-sol. The photofrin release revel of PF-PEG-Lip was lower than that of PF-Lip. In conclusion, the phototoxicity of PF-PEG-Lip was significantly higher than that of PF-sol or PF-Lip. It is expected that formation of a fixed aqueous layer on the liposome membrane by PEGylation physically changed it into the stable state of PF-PEG-Lip. [Copyright &y& Elsevier]

Summary: Developments in the fluorescence detection of cancer aim either to distinguish tissue autofluorescence from that of injected fluorophores or to exploit differences in autofluorescent spectra of normal versus transforming, premalignant and malignant tissue. This study evaluates the utility of autofluorescence and Photofrin-induced fluorescence imaging and spectroscopy to distinguish tissue transformation associated with early malignant change in the oral cavity. The model of tissue transformation used was that induced by the carcinogen DMBA in the hamster buccal cheek pouch. Fluorescence spectra were obtained using a high-sensitivity fiber optic spectrometer, while imaging was performed using a Multispectral Fluorescence Guidance (MFG) system designed for use in intraoperative fluorescence imaging during photodynamic therapy. The results demonstrate that Photofrin fluorescence can be used to predict the pathologic state of tissue, the fluorescence intensity being directly proportional to the degree of malignant transformation. Autofluorescence detection measured two parameters that are altered by transformation stage: the red/green fluorescence ratio and the total fluorescence intensity. The most striking feature was the change in the latter in malignant tissue. The MFG imaging device performed as well as spectroscopy: the sensitivity and specificity for the imaging system were 65% and 90% for autofluorescence and 87% and 85% with Photofrin. This indicates that either the autofluorescence intensity index of the tissue or the Photofrin-induced fluorescence may provide a good parameter for the “first approximation” characterization of the tissue. [Copyright &y& Elsevier]

Summary: Gorlin syndrome (naevoid basal cell carcinoma syndrome) is a genetically linked disorder characterized by the development of multiple basal cell carcinomas (BCCs) throughout life. Cumulative surgery, cryotherapy and other conventional interventions can result in significant disfigurement by middle age. Radiotherapy is contra-indicated because the mutated gene underlying the syndrome, ‘PTCH’, increases sensitivity to ionising radiation, so there is significant likelihood of inducing further tumours in and around the irradiated area. Photodynamic therapy offers a non-invasive treatment option for patients with this condition, with the added advantage of causing minimal scarring. [Copyright &y& Elsevier]

Summary: Photodynamic therapy is a very important technique for the eradication of widespread oesophageal mucosal disease which has the potential to degenerate to cancer. Patients unsuitable or unwilling to undergo radical therapy can be cured using photodynamic therapy. We predominantly treat patients with high-grade dysplasia in Barrett''s oesophagus. Lesions that are visible macroscopically are removed using endoscopic mucosal resection. The remaining area is then treated in 5cm segments at 3 monthly intervals with separate photosensitisation using endoscopic photodynamic therapy. [Copyright &y& Elsevier]

Summary: Background: Treatment of basal cell carcinomas in naevoid basal cell carcinoma syndrome (NBCCS) poses several challenges. The sheer numbers of such lesions in these patients makes traditional therapeutic modalities like surgery, impractical. Topical photodynamic therapy (PDT) with δ-5-amino levulinic acid has increasingly been recognised as and safe and effective choice in the treatment of BCC. The probability of local control of BCC treated by PDT depends strongly on lesion thickness, thick nodular lesions being less responsive. Response to treatment is monitored by the reduction in the lesional size, but histopathological confirmation of regression is often required. Method: We used systemic photodynamic therapy with Porfimer Sodium (Photofrin®, Axcan Pharma Inc., Quebec, Canada), a systemic photosensitizer for treating multiple BCC in seven patients with NBCCS. Treatment response was monitored using a high resolution 20MHz ultrasound. Results: There was a substantial reduction in the number of superficial basal cell carcinomas with complete US regression after one treatment. A 74.2% reduction was seen in the size of thick lesions treated with external light. Thick nodular lesions in two patients treated with interstitial optical diffuser fibres in addition to external light showed 87.6% reduction in size as measured by high resolution ultrasound. Conclusions: Our preliminary results indicate that systemic photodynamic therapy using Photofrin and external light either alone or with interstitial optical diffuser fibres; may be effective in treatment of multiple, thick and nodular BCC lesions in Naevoid basal cell carcinoma syndrome. Further studies are needed to confirm our observations. We found high resolution ultrasound an effective alternative to histopathological analysis in monitoring the response to treatment. [Copyright &y& Elsevier]

Summary: Esophageal cancer, when detected at an early stage, has a very good probability of being eradicated by surgery or radiotherapy. However, less aggressive treatments also tend to provide high rates of cure without the side effects of radical surgery or radiotherapy. Among them, photodynamic therapy and endoscopic mucosal resection have been experienced as alternative techniques for mucosal ablation in patients with superficial squamous-cell carcinoma (SCC) of the esophagus, or high-grade dysplasia and early stage adenocarcinoma arising in Barrett''s esophagus. We report on the results of our clinical experience with photodynamic therapy and discuss about its advantages and limitations. We also present a pre-clinical study, which had evaluated the feasibility, efficacy, and safety of a promising new method of endoscopic mucosal resection (EMR) based on the use of a modified rigid esophagoscope. The animal model chosen was the sheep because of its similarities with humans regarding the thickness and histologic structure of the esophagus. This new resection modality offers a promising approach in comparison with other options currently available, namely EMRs performed with flexible gastroscopes. It appears to be superior in terms of the size of the resected specimen, the precision and regularity of the resection depth, and the accuracy of histological diagnosis with safety margins. [Copyright &y& Elsevier]

Photodynamic therapy (PDT) has been established as a potent and less invasive treatment for gastrointestinal tumors. The aim of the present study was to investigate whether or not liposomalization of the photosensitizer enhanced the therapeutic efficacy of PDT. Photofrin (PF) was entrapped in multilammelar liposomes. Mice implanted with a human gastric cancer xenograft, were divided into a PF group and a liposomal photofrin (LPF) group and intravenously administered 10 mg/kg of PF or LPF (as a dose of PF), respectively. At 8 h after injection PF level in tumor tissue in the LPF group was significantly higher level by 2.4-fold of that in the PF group, whereas the PF levels in the skin were almost equal. Irradiation was performed with the excimer dye laser at 150 mW/cm2, total dose 40 J, at 8 h after PF or LPF administration. The results revealed that the volume of necrotic tumor tissue was significantly higher in the LPF group than in the PF group. The apoptotic index of the tumor was also significantly higher in the LPF group. In conclusion, the liposomalization of the photosensitizer increased its tumor accumulation, with a resulting enhancement of the therapeutic effect of PDT. [Copyright &y& Elsevier]

We have examined the possible role of the stress-activated JNK and p38 protein kinases in cellular sensitivity following Photofrin-mediated photodynamic therapy (PDT). Previously we reported that immortalized Li–Fraumeni syndrome (LFS) cells are more resistant to Photofrin-mediated PDT compared to normal human fibroblasts (NHF) at equivalent cellular Photofrin levels. In the current work we report that Photofrin-mediated PDT increased the activity of JNK1 and p38 within 30 min in both cell types. However, the increased activity of JNK1 and p38 was transient in the sensitive NHF cells and returned back to near basal levels by 3 h after PDT. In contrast, the resistant LFS cells exhibited a more prolonged activation of JNK and p38, which lasted for at least 11 h and 7 h after PDT, respectively. Blocking of the p38 pathway in LFS cells by transient infection with a recombinant adenovirus expressing a dominant negative mutant of p38 or in HeLa cells by stable transfection with a dominant negative mutant of p38 had no effect on cell survival following PDT. These data suggest that although Photofrin-mediated PDT is able to induce JNK1 and p38 in human cells, the p38 pathway alone does not play a major role in the sensitivity of LFS cells to Photofrin-mediated PDT. [Copyright &y& Elsevier]

Photodynamic therapy (PDT) is a therapeutic modality involving the use of a photosensitizing agent activated by light to destroy tumor cells. Over the past 25 years, PDT has been shown useful in the treatment of actinic keratoses and certain nonmelanoma skin cancers, such as Bowen’s disease and basal cell carcinoma. We review the current data available for PDT with systemic photofrin and topical 5-aminolevulinic acid (ALA). PDT offers many advantages including its non-invasiveness and its ability to treat multiple lesions simultaneously and is, therefore, an interesting alternative for treating certain skin malignancies. [Copyright &y& Elsevier]

Summary: Objective/Hypothesis: To analyze vocal fold vibration after photofrin-mediated photodynamic therapy (PDT) for the treatment of Tis and T1N0M0 squamous cell carcinoma (SqCCa) tumors of the larynx. It was hypothesized that key attributes of vocal fold vibration would return to baseline within 1–6 months of treatment. Study Design: Retrospective. Methods: Laryngovideostroboscopic data were retrospectively analyzed for eight patients with Tis-T1N0M0 SqCCa tumors of the larynx treated with photofrin-mediated PDT. Baseline and posttreatment videostroboscopy images of select vibratory characteristics of the vocal folds were randomized and analyzed by a speech-language pathologist and fellowship-trained laryngologist specializing in voice disorders. Results: Significant improvement in mucosal wave (P =0.003) and amplitude of vibration (P =0.004) occurred at greater than or equal to 20 weeks post-PDT compared with baseline. Comparing results within 5 weeks postprocedure to 10–19-weeks postprocedure revealed significant improvement in amplitude of vibration (P =0.013) and nonvibrating portion of the vocal fold (P =0.020). Comparing results within 5-weeks postprocedure to 20 or more weeks postprocedure revealed significant improvement in amplitude of vibration (P =0.001), mucosal wave (P =0.001), and nonvibrating portion of the effected fold (P =0.001). Conclusion: Photofrin-mediated PDT allows for preservation of function and structure of the larynx without systemic toxicity; however, it may take 4–5 months or more for key vibratory characteristics of the vocal folds to recover posttreatment. [Copyright &y& Elsevier]

• The study was the combination of PDT and an immunoadjuvant glycated chitosan (GC) on murine EMT6 and 4T1 tumor. • To investigate the anti-tumor and immune efficacy of the combination. • The study suggested that the combination of PDT and GC induces a better tumor control and survival. • The combination had a higher induced nitric oxide synthase (iNOs) and HSP70 expression, and an increased apoptosis rate and also a stronger infiltration of activated lymphocytes. • The combination of PDT and GC can amplify antitumor immune response, introducing a long term and systemic immunity. Metastases and recurrence of cancer are the main causes of failure and death. Induction of a long-term tumor specific immunity seems to be a great strategy to deal with this challenge. Laser immunotherapy (LIT), using immunomodulatory techniques in combination with photodynamic therapy (PDT), so as to enhance an already robust immune response, has been proposed and investigated by numerous researchers. In our study, mice bearing EMT6 breast tumors and 4T1 metastatic breast tumors were addressed in various permutations of the different components in LIT. The survival rates and the tumor growth curve of EMT6 breast tumors bearing mice were analyzed. We compared the level of inflammatory reaction, cell apoptosis and activated immune cells infiltration of local tumors. We validated the systemic effect of LIT through the 4T1 metastatic breast tumors bearing mice. The results not only proved that concomitant with Glycated chitosan (GC) can improve the effect of inhibiting the tumor growth, improving survival, enhancing local inflammatory reaction and attracting acted immune cells to tumor by photodynamic therapy with Photofrin, but also intuitively proved the systemic effect and long-term effect of LIT. [ABSTRACT FROM AUTHOR]

• Saffron can efficiently be used to reduce the photosensitivity reaction of Photosensitizers. • Saffron did not have phototoxicity on Red Blood Cells (RBCs) and S taphylococcusaureus Bacteria (STB). • Saffron can be used as an antioxidant food supplement. • Gompertz function is an appropriate mathematical model for survival rate curves of the RBCs and the S taphylococcusaureus Bacteria. The photosensitivity reaction which appears after a Photodynamic therapy treatment session is a challenge that needs further investigation. The goal of this research is to evaluate the possibility of using saffron to reduce or control this photosensitivity reaction and to present mathematical modeling of the cell survival curves and their dependency on saffron concentration. Red blood cells (RBC) and Staphylococcus aureus Bacteria (STB) were used as targets in this study. The Photosensitivity of Rose Bengali, Methylene Blue, and Photofrin independently and incorporated with saffron was investigated for continued irradiation at different Saffron concentrations. Gompertz's function was used to fit the survival curve parameters. The 50% cell survival rate was fit to an empirical formula based on Saffron concentrations. Saffron inhibits the photosensitivity reaction of the three photosensitizers and causes a significant increase in the 50% survival rate time (t 50) for RBC's and STB. Saffron didn't show phototoxicity when incubated alone with RBC's and STB. The survival curve parameters of the RBCs and STB showed a good fit to the Gompertz function. Saffron concentration is related to the RBC's t 50 based on power dependency of 0.56, 0.38 and 0.31 for Photofrin, Methylene Blue and Rose Bengali respectively and 0.1 on STB for Rose Bengali. Saffron can efficiently be used to reduce the photosensitivity reaction of Photosensitizers after a PDT treatment session. Gompertz function was found to be an appropriate mathematical model for survival rate curves. The t 50 and the saffron concentration are well related through a power dependence empirical formula. [ABSTRACT FROM AUTHOR]

Summary: We have considerable experience in the use of both ALA and Photofrin-induced photodynamic therapy in the treatment of Barrett''s oesophagus (with and without dysplasia) and both early and advanced oesophageal carcinoma. The drugs used and the techniques vary depending on the condition being treated. The techniques and doses used for the various conditions are outlined here. [Copyright &y& Elsevier]