Y. Istomin, M. A. Kaplan, S. V. Shliakhtsin, T. P. Lapzevich, D. A. Cerkovsky, Ludmila N. Marchanka, A. Fedulov, T. Trukhachova
{"title":"Immediate and long-term efficacy and safety of photodynamic therapy with Photolon (Fotolon): a seven-year clinical experience","authors":"Y. Istomin, M. A. Kaplan, S. V. Shliakhtsin, T. P. Lapzevich, D. A. Cerkovsky, Ludmila N. Marchanka, A. Fedulov, T. Trukhachova","doi":"10.1117/12.823840","DOIUrl":"https://doi.org/10.1117/12.823840","url":null,"abstract":"The purpose of the present study was to summarize data on the long-term efficacy of photodynamic therapy (PDT) with Photolon in patients with malignant tumors of various types and localizations. The data obtained show that PDT with Photolon is a highly effective therapeutic modality for the treatment of skin tumors, cervical intraepithelial neoplasias, lung cancers, disseminated forms of melanoma, primary and metastatic brain tumors, several ophthalmologic diseases. This paper provides a review of most illustrative studies of the application of PDT with Photolon for the treatment of different oncological and non-oncological diseases performed in leading clinical centers of the Republic of Belarus and Russia.","PeriodicalId":267589,"journal":{"name":"World Congress of the International Photodynamic Association","volume":"115 20 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2009-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126372292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Ito, H. Matsuo, Tsukasa Suenari, Takuro Kajihara, Takehiro Kimura, S. Miyoshi, S. Ogawa, T. Arai
{"title":"The new application of photosensitization reaction to atrial fibrillation treatment: mechanism and demonstration of non-thermal electrical conduction block with porcine heart","authors":"A. Ito, H. Matsuo, Tsukasa Suenari, Takuro Kajihara, Takehiro Kimura, S. Miyoshi, S. Ogawa, T. Arai","doi":"10.1117/12.822924","DOIUrl":"https://doi.org/10.1117/12.822924","url":null,"abstract":"We have proposed non-thermal electrical conduction block for atrial fibrillation treatment by the photosensitization reaction, in which the interval time between the photosensitizer injection and irradiation is less than tenth of that in conventional way. To study the mechanism of photosensitization reaction-induced electrical conduction block, intracellular Ca2+ concentration change in rat myocardial cells was measured by fluorescent Ca2+ indicator Fluo-4 AM with confocal laser microscopy. Measured rapid increase in the fluorescence intensity and a change in cell morphology indicated that cell membrane damage; that is Ca2+ influx and eventually cell death caused by the photosensitization reaction. To demonstrate myocardial electrical conduction block induced by the photosensitization reaction, surgically exposed porcine heart under deep anesthesia was used. The myocardial tissue was paced with a stimulation electrode. The propagated electrical signals were measured by bipolar electrodes at two different positions. Thirty minutes after the injection of 5-10 mg/kg Porfimer sodium or Talaporfin sodium, the red laser light was irradiated to the tissue point by point crossing the measuring positions by the total energy density of less than 200 J/cm2. The electrical signal conduction between the measuring electrodes in the myocardial tissue was delayed by each irradiation procedure. The electrical conduction delay corresponded to the block line length was obtained. These results demonstrated the possibility of non-thermal electrical conduction block for atrial fibrillation treatment by the photosensitization reaction.","PeriodicalId":267589,"journal":{"name":"World Congress of the International Photodynamic Association","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2009-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121826950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhancing protoporphyrin IX-induced PDT","authors":"A. Curnow, A. Pye, S. Campbell","doi":"10.1117/12.822241","DOIUrl":"https://doi.org/10.1117/12.822241","url":null,"abstract":"Photodynamic therapy (PDT) using porphyrin precursors is commonly used in dermatology. Evidence indicates that good clinical outcomes (associated with excellent cosmesis) can be achieved in superficial precancers and basal cell carcinoma (BCC), however, efficacy appears less favorable for thicker nodular BCC (nBCC) unless multiple PDT treatment cycles are performed. Enhancement is therefore required if nBCC lesions are to be treated effectively with a single PDT treatment. The most common technique currently being routinely employed clinically is the use of aminolevulinic acid (ALA) esters (usually methyl (MAL) or hexyl (HAL)). Standard dermatological PDT employing these porphyrin precursors already manipulates the normal heme biosynthesis pathway resulting in a temporary accumulation of the natural photosensitizer, protoporphyrin IX (PpIX). Further manipulation using iron chelating agents is possible however. In normal and malignant human cells in vitro, the novel iron chelating agent CP94 produced greater PPIX fluorescence when administered with ALA or MAL than either congener produced alone. CP94 was also significantly more effective than the clinically established iron chelating agent desferrioxamine (DFO). Topical application of ALA+CP94 to clinical nBCC lesions was a simple and safe treatment modification which produced a significant increase in clinical clearance when CP94 was included in the cream.","PeriodicalId":267589,"journal":{"name":"World Congress of the International Photodynamic Association","volume":"212 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2009-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115973652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Gill, S. Gross, B. Greenwald, L. Hemminger, H. Wolfsen
{"title":"Burn, freeze, or photo-ablate?: comparative symptom profile in Barrett's dysplasia patients undergoing endoscopic ablation","authors":"K. Gill, S. Gross, B. Greenwald, L. Hemminger, H. Wolfsen","doi":"10.1117/12.822827","DOIUrl":"https://doi.org/10.1117/12.822827","url":null,"abstract":"Background: There are few data available comparing endoscopic ablation methods for Barrett's esophagus with high-grade dysplasia (BE-HGD). Objective: To determine differences in symptoms and complications associated with endoscopic ablation. Design: Prospective observational study. Setting: Two tertiary care centers in USA. Patients: Consecutive patients with BE-HGD Interventions: In this pilot study, symptoms profile data were collected for BE-HGD patients among 3 endoscopic ablation methods: porfimer sodium photodynamic therapy, radiofrequency ablation and low-pressure liquid nitrogen spray cryotherapy. Main Outcome Measurements: Symptom profiles and complications from the procedures were assessed 1-8 weeks after treatment. Results: Ten BE-HGD patients were treated with each ablation modality (30 patients total; 25 men, median age: 69 years (range 53-81). All procedures were performed in the clinic setting and none required subsequent hospitalization. The most common symptoms among all therapies were chest pain, dysphagia and odynophagia. More patients (n=8) in the porfimer sodium photodynamic therapy group reported weight loss compared to radio-frequency ablactation (n=2) and cryotherapy (n=0). Four patients in the porfimer sodium photodynamic therapy group developed phototoxicity requiring medical treatment. Strictures, each requiring a single dilation, were found in radiofrequency ablactation (n=1) and porfimer sodium photodynamic therapy (n=2) patients. Limitations: Small sample size, non-randomized study. Conclusions: These three endoscopic therapies are associated with different types and severity of post-ablation symptoms and complications.","PeriodicalId":267589,"journal":{"name":"World Congress of the International Photodynamic Association","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2009-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133774139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ulysses W. Sallum, Xiang Zheng, S. Verma, T. Hasan
{"title":"Exploiting bacterial drug resistance: a single construct for the diagnosis and treatment of drug resistant infections","authors":"Ulysses W. Sallum, Xiang Zheng, S. Verma, T. Hasan","doi":"10.1117/12.828202","DOIUrl":"https://doi.org/10.1117/12.828202","url":null,"abstract":"β-lactamase enzyme-activated photosensitizer (β-LEAP). We aim to exploit drug resistance mechanisms to selectively release photosensitizers (PSs) for a specific photodynamic antimicrobial effect and reduced host tissue damage. Consequently, the fluorescence emission intensity of the PSs increases and allows for the detection of enzyme activity. In this work we sought to evaluate β-LEAP for use as a sensitive molecular probe. We have reported the enzyme specific antibacterial action of β-LEAP. Here we report the use of β-LEAP for the rapid functional definition of a β-lactamase.","PeriodicalId":267589,"journal":{"name":"World Congress of the International Photodynamic Association","volume":"30 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2009-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131497567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Lee, K. Galbally-Kinney, M. Hinds, J. O’Hara, B. Pogue, A. Liang, T. Hasan, S. Davis
{"title":"A singlet oxygen monitor as an in vivo photodynamic therapy dosimeter","authors":"S. Lee, K. Galbally-Kinney, M. Hinds, J. O’Hara, B. Pogue, A. Liang, T. Hasan, S. Davis","doi":"10.1117/12.823030","DOIUrl":"https://doi.org/10.1117/12.823030","url":null,"abstract":"In this paper we describe the development and testing of instruments to measure singlet molecular oxygen produced by the photodynamic process. Singlet oxygen is an active species in photodynamic therapy, and we are developing two instruments for PDT researchers with the goal of a real-time dosimeter for singlet oxygen. We discuss both an ultrasensitive point sensor, and an imaging system that provides simultaneous 2D maps of the photosensitizer fluorescence and the singlet oxygen emission. Results of in vitro tests to characterize the sensors and preliminary in vivo results are presented.","PeriodicalId":267589,"journal":{"name":"World Congress of the International Photodynamic Association","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2009-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128523415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Johansson, H. Stepp, W. Beyer, T. Pongratz, R. Sroka, M. Bader, M. Kriegmair, D. Zaak, R. Waidelich, A. Karl, A. Hofstetter, C. Stief, R. Baumgartner
{"title":"Photodynamic management of bladder cancer","authors":"A. Johansson, H. Stepp, W. Beyer, T. Pongratz, R. Sroka, M. Bader, M. Kriegmair, D. Zaak, R. Waidelich, A. Karl, A. Hofstetter, C. Stief, R. Baumgartner","doi":"10.1117/12.828315","DOIUrl":"https://doi.org/10.1117/12.828315","url":null,"abstract":"Bladder cancer (BC) is among the most expensive oncological diseases. Any improvement in diagnosis or therapy carries a high potential for reducing costs. Fluorescence cystoscopy relies on a selective formation of Protoporphyrin IX (PpIX) or more general photoactive porphyrins (PAP) in malignant urothelium upon instillation of 5-aminolevulinic acid (5-ALA) or its hexyl-derivative h-ALA. Fluorescence cystoscopy equipment has been developed with the aim to compensate for the undesired distortion caused by the tissue optical properties by displaying the red fluorescence simultaneously with the backscattered blue light. Many clinical studies proved a high sensitivity in detecting flat carcinoma in situ and small papillary malignant tumours. As a result, recurrence rates were significantly decreased in most studies. The limitation lies in a low specificity, caused by false positive findings at inflamed bladder wall. Optical coherence tomography (OCT) is currently being investigated as a promising tool to overcome this limitation. H-ALA-PDT (8 or 16 mM h-ALA in 50 ml instillation for 1-2 h, white light source, catheter applicator) has recently been investigated in a phase I study. 17 patients were applied 100 J/cm2 (3 patients received incrementing doses of 25 - 50 - 100 J/cm2) during approx. 1 hour irradiation time in 3 sessions, 6 weeks apart. PDT was performed without any technical complications. Complete photobleaching of the PpIX-fluorescence, as intended, could be achieved in 43 of 45 PDT-sessions receiving 100 J/cm2. The most prominent side effects were postoperative urgency and bladder pain, all symptoms being more severe after 16 mM h-ALA. Preliminary evaluation shows complete response assessed at 3 months after the third PDT-session (i.e. 6 months after first treatment) in 9 of 12 patients. 2 of these patients were free of recurrence until final follow-up at 84 weeks.","PeriodicalId":267589,"journal":{"name":"World Congress of the International Photodynamic Association","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2009-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133110268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Rajagopalan, A. Karwa, P. Lusiak, K. Srivastava, A. Poreddy, R. Pandurangi, K. Galen, W. Neumann, Gary E. Cantrell, R. Dorshow
{"title":"Novel type 1 photosensitizers: viability of leukemia cells exposed to reactive intermediates generated in situ by in vitro photofragmentation","authors":"R. Rajagopalan, A. Karwa, P. Lusiak, K. Srivastava, A. Poreddy, R. Pandurangi, K. Galen, W. Neumann, Gary E. Cantrell, R. Dorshow","doi":"10.1117/12.822840","DOIUrl":"https://doi.org/10.1117/12.822840","url":null,"abstract":"Photodynamic therapy of tumors involving Type 2 photosenstizers has been conspicuously successful, but the Type 1 process, in contrast, has not received much attention despite its considerable potential. Accordingly, several classes of molecules containing fragile bonds such as azido (-N=N=N), azo (-N=N-), sulfenato (-S-O-) and oxaza (-N-O-) functional groups that produce reactive intermediates such as radicals and nitrenes upon photoexcitation were prepared and tested for cell viability using U397 leukemia cell line. The azido photosensitizer was conjugated to leukemia cell binding peptide, SFFWRLS, for targeted cell viability study. The cells were incubated with the photosensitizer at various concentrations, and were illuminated for 5, 10, and 20 minutes. The results show that all the photosensitizers caused cell death compared to the controls when exposed to both the photosensitizers and light. Most importantly, selective cell death was observed with the azido peptide conjugate 6, which clearly demonstrates that these Type 1 sensitizers are useful for phototherapeutic applications.","PeriodicalId":267589,"journal":{"name":"World Congress of the International Photodynamic Association","volume":"44 2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2009-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116934638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Berkovitch, A. Nudelman, B. Ehenberg, A. Rephaeli, Z. Malik
{"title":"Novel multifunctional acyloxyalkyl ester prodrugs of 5-aminolevulinic acid display improved anticancer activity dependent on photoactivation","authors":"G. Berkovitch, A. Nudelman, B. Ehenberg, A. Rephaeli, Z. Malik","doi":"10.1117/12.822703","DOIUrl":"https://doi.org/10.1117/12.822703","url":null,"abstract":"New approaches to PDT using multifunctional 5-aminolevulinic acid (ALA) based prodrugs activating mutual routes of toxicity are described. We investigated the mutual anti-cancer activity of ALA prodrugs which upon metabolic hydrolysis by unspecific esterases release ALA, formaldehyde or acetaldehye and the histone deacetylase inhibitor (HDACI) butyric acid. The most potent prodrug in this study was butyryloxyethyl 5-amino-4-oxopentanoate (AN-233) that stimulated a rapid biosynthesis of protoporphyrin IX (PpIX) in human glioblastoma U-251 cells and generated an efficient photodynamic destruction. AN-233 induced a considerable high level of intracellular ROS in the cells following light irradiation, reduction of mitochondrial activity, dissipation of the mitochondrial membrane potential resulting in necrotic and apoptotic cell death. The main advantage of AN-233 over ALA stems from its ability to induce photodamage at a significantly lower dose than ALA.","PeriodicalId":267589,"journal":{"name":"World Congress of the International Photodynamic Association","volume":"73 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2009-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"120977285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular mechanisms associated with ALA-PDT of brain tumor cells","authors":"O. Alqawi, M. Espiritu, G. Singh","doi":"10.1117/12.823018","DOIUrl":"https://doi.org/10.1117/12.823018","url":null,"abstract":"Previous studies have shown that low-dose PDT using 5-aminolevulinic acid (ALA)-induced photoporphyrin IX (PpIX) can induce apoptosis in tumor cells without causing necrosis. In this study we investigated the molecular mechanisms associated with apoptosis after ALA-PDT treatment in two brain glioma cell lines: human U87, and rat CNS-1cells. We used high energy light at a short time (acute PDT) and low energy light at a long time of exposure (metronomic PDT) to treat both cell lines. The cells were treated with 0.25 mM ALA at 5 joules for energy. We found that CNS-1 cells were more resistant to ALA-PDT than U87 cells when treated by both acute and metronomic PDT. To screen possible apoptosis mechanisms associated with acute and metronomic PDT, microarray analysis of gene expression was performed on RNA from glioblastoma cells treated with either acute or metronomic ALA-PDT. Within the set of genes that were negatively or positively regulated by both treatments are tumor necrosis factor receptors. The expression of TNF receptors was investigated further by RT-PCR and western blotting. The apoptosis mechanism of the cell death occurred through different pathways including BCL-2 and TNF receptors, and in part caused by cleaving caspase 3. Interestingly, metronomic ALA-PDT inhibited the expression of LTβR and the transcription factor NFκB. This inhibition was ALA concentration dependent at low concentrations.","PeriodicalId":267589,"journal":{"name":"World Congress of the International Photodynamic Association","volume":"70 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2009-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127129833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}