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Photomedicine and Laser Surgery Aug 2013Photodynamic therapy (PDT) as a medical treatment for cancers is an increasing practice in clinical settings, as new photosensitizing chemicals and light source... (Review)
Review
OBJECTIVE
Photodynamic therapy (PDT) as a medical treatment for cancers is an increasing practice in clinical settings, as new photosensitizing chemicals and light source technologies are developed and applied. PDT involves dosing patients with photosensitizing drugs, and then exposing them to light using a directed energy device in order to manifest a therapeutic effect. Healthcare professionals providing PDT should be aware of potential occupational health and safety hazards posed by these treatment devices and photosensitizing agents administered to patients.
MATERIALS AND METHODS
Here we outline and identify pertinent health and safety considerations to be taken by healthcare staff during PDT procedures.
RESULTS
Physical hazards (for example, non-ionizing radiation generated by the light-emitting device, with potential for skin and eye exposure) and chemical hazards (including the photosensitizing agents administered to patients that have the potential for exposure via skin, subcutaneous, ingestion, or inhalation routes) must be considered for safe use of PDT by the healthcare professional.
CONCLUSIONS
Engineering, administrative, and personal protective equipment controls are recommendations for the safe use and handling of PDT agents and light-emitting technologies.
Topics: Aminolevulinic Acid; Dihematoporphyrin Ether; Hematoporphyrin Photoradiation; Humans; Intense Pulsed Light Therapy; Lasers; Occupational Exposure; Occupational Health; Photochemotherapy; Photosensitizing Agents; Porphyrins; Safety Management; Verteporfin
PubMed: 23859750
DOI: 10.1089/pho.2013.3496 -
The Journal of Membrane Biology Oct 2013The influence of electroporation on the Photofrin uptake and distribution was evaluated in the breast adenocarcinoma cells (MCF-7) and normal Chinese hamster ovary cells...
The influence of electroporation on the Photofrin uptake and distribution was evaluated in the breast adenocarcinoma cells (MCF-7) and normal Chinese hamster ovary cells (CHO) lacking voltage-dependent channels in vitro. Photofrin was used at a concentration of 5 and 25 μM. The uptake of Photofrin was assessed using flow cytometry and fluorescence microscopy methods. Cells viability was evaluated with crystal violet assay. Our results indicated that electropermeabilization of cells, in the presence of Photofrin, increased the uptake of the photosensitizer. Even at the lowest electric field intensity (700 V/cm) Photofrin transport was enhanced. Flow cytometry results for MCF-7 cells revealed ~1.7 times stronger fluorescence emission intensity for cells exposed to Photofrin and electric field of 700 V/cm than cells treated with Photofrin alone. Photofrin was effective only when irradiated with blue light. Our studies on combination of photodynamic reaction with electroporation suggested improved effectiveness of the treatment and showed intracellular distribution of Photofrin. This approach may be attractive for cancer treatment as enhanced cellular uptake of Photofrin in MCF-7 cells can help to reduce effective dose of the photosensitizer and exposure time in this type of cancer, diminishing side effects of the therapy.
Topics: Animals; Antineoplastic Agents; Breast Neoplasms; CHO Cells; Cell Survival; Cricetinae; Cricetulus; Dihematoporphyrin Ether; Electroporation; Female; Humans; MCF-7 Cells; Photosensitizing Agents
PubMed: 23546012
DOI: 10.1007/s00232-013-9533-z -
Clinical Endoscopy Jan 2013This paper reviews the use of photodynamic therapy (PDT) in patients with Barrett's esophagus and esophageal carcinoma. We describe the history of PDT, mechanics,...
This paper reviews the use of photodynamic therapy (PDT) in patients with Barrett's esophagus and esophageal carcinoma. We describe the history of PDT, mechanics, photosensitizers for PDT in patients with esophageal disease. Finally, we discuss its utility and limitations in this setting.
PubMed: 23423151
DOI: 10.5946/ce.2013.46.1.30 -
PloS One 2013Glioblastoma is the most common malignant brain tumor in humans. We explored the molecular mechanisms how the efficacy of photofrin based photodynamic therapy (PDT) was...
Photofrin based photodynamic therapy and miR-99a transfection inhibited FGFR3 and PI3K/Akt signaling mechanisms to control growth of human glioblastoma In vitro and in vivo.
Glioblastoma is the most common malignant brain tumor in humans. We explored the molecular mechanisms how the efficacy of photofrin based photodynamic therapy (PDT) was enhanced by miR-99a transfection in human glioblastoma cells. Our results showed almost similar uptake of photofrin after 24 h in different glioblastoma cells, but p53 wild-type cells were more sensitive to radiation and photofrin doses than p53 mutant cells. Photofrin based PDT induced apoptosis, inhibited cell invasion, prevented angiogenic network formation, and promoted DNA fragmentation and laddering in U87MG and U118MG cells harvoring p53 wild-type. Western blotting showed that photofrin based PDT was efficient to block the angiogenesis and cell survival pathways. Further, photofrin based PDT followed by miR-99a transfection dramatically increased miR-99a expression and also increased apoptosis in glioblastoma cell cultures and drastically reduced tumor growth in athymic nude mice, due to down regulation of fibroblast growth factor receptor 3 (FGFR3) and PI3K/Akt signaling mechanisms leading to inhibition of cell proliferation and induction of molecular mechanisms of apoptosis. Therefore, our results indicated that the anti-tumor effects of photofrin based PDT was strongly augmented by miR-99a overexpression and this novel combination therapeutic strategy could be used for controlling growth of human p53 wild-type glioblastomas both in vitro and in vivo.
Topics: Apoptosis; Blotting, Western; Cell Line, Tumor; Comet Assay; Dihematoporphyrin Ether; Flow Cytometry; Glioblastoma; Humans; In Vitro Techniques; MicroRNAs; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Photochemotherapy; Proto-Oncogene Proteins c-akt; Real-Time Polymerase Chain Reaction; Receptor, Fibroblast Growth Factor, Type 3; Signal Transduction; Transfection
PubMed: 23409016
DOI: 10.1371/journal.pone.0055652 -
Advances in Clinical and Experimental... 2012Melanoma is the most severe of skin neoplasms as it may grow rapidly and metastasize. The application of photodynamic therapy (PDT) opens up new prospects in the...
BACKGROUND
Melanoma is the most severe of skin neoplasms as it may grow rapidly and metastasize. The application of photodynamic therapy (PDT) opens up new prospects in the treatment of this tumor. Numerous studies suggest that the exposure of tumor cells to PDT can lead to cellular and molecular mechanisms which mediate oxidative stress in cells.
OBJECTIVES
The aim of this study was to evaluate in vitro the influence of photodynamic therapy on the human melanoma Me45 cell line.
MATERIAL AND METHODS
Photofrin (Ph) was used as a photosensitizer.
RESULTS
Viability studies have shown that there are significant differences between cells after PDT and cells without irradiation. After 24 hours of incubation with a 20 microg/ml concentration of Ph and with irradiation, less than 20% of the cells survived. In the control (without PDT), 65% of the cells survived.
CONCLUSIONS
The mitochondrial localization of Ph is significant, as it may lead to disturbances of mitochondrial transmembrane potential and finally to apoptotic cell death. The expressions of manganese superoxide dismutase and heme oxygenase and the level of carbonyl and thiol groups are indicating factors for oxidative stress in Me45 cells.
Topics: Apoptosis; Cell Line, Tumor; Cell Survival; Dihematoporphyrin Ether; Heme Oxygenase-1; Humans; Melanoma; Mitochondria; Oxidative Stress; Photochemotherapy; Photosensitizing Agents; Protein Carbonylation; Skin Neoplasms; Superoxide Dismutase; Time Factors
PubMed: 23214281
DOI: No ID Found -
Photodiagnosis and Photodynamic Therapy Dec 2012In patients with unresectable cholangiocarcinoma, photodynamic therapy (PDT) with porfimer sodium promotes biliary drainage and may improve survival and quality of life.
BACKGROUND
In patients with unresectable cholangiocarcinoma, photodynamic therapy (PDT) with porfimer sodium promotes biliary drainage and may improve survival and quality of life.
AIM
To prospectively evaluate the safety and efficacy of PDT in patients with locally advanced biliary tract carcinoma.
METHODS
Eligible patients had unresectable, histologically confirmed disease, a Karnofsky performance status of ≥30% and life expectancy >12 weeks. Patients received 2mg/kg i.v. of porfimer sodium, followed by endobiliary laser activation and stent replacement 48 h later. Patients were assessed clinically and radiologically before treatment and on day 28, and followed up thereafter at three-monthly intervals until death.
RESULTS
36 patients were entered over an 18 months period: 14 males, 22 females, with a median age of 65 (30-79)yr and performance status of 80 (50-100). PDT was technically successful in all cases and was generally well tolerated; there was no grade 4 toxicity and no treatment-associated mortality. The median survival was 12 (1-84) months.
CONCLUSIONS
Porfimer sodium PDT can be delivered safely to patients with biliary tract cancer and is suitable for testing in phase III studies (UKCRN ID 1218).
Topics: Adult; Aged; Biliary Tract Neoplasms; Bilirubin; Biomarkers, Tumor; Dihematoporphyrin Ether; Female; Humans; Karnofsky Performance Status; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Prospective Studies; Quality of Life
PubMed: 23200007
DOI: 10.1016/j.pdpdt.2012.03.005 -
Cancer Biology & Therapy Jan 2013Tumor relapse and tumor cell repopulation has been explained partially by the drug-free break period between successive conventional treatments. Strategies to overcome...
Tumor relapse and tumor cell repopulation has been explained partially by the drug-free break period between successive conventional treatments. Strategies to overcome tumor relapse have been proposed, such as the use of chemotherapeutic drugs or radiation in small, frequent fractionated doses without an extended break period between treatment intervals. Yet, tumors usually acquire resistance and eventually escape the therapy. Several mechanisms have been proposed to explain the resistance of tumors to therapy, one of which involves the cancer stem cell or tumor-initiating cell (TIC) concept. TICs are believed to resist many conventional therapies, in part due to their slow proliferation and self-renewal capacities. Therefore, emerging efforts to eradicate TICs are being undertaken. Here we show that treatment with Photofrin II, among the most frequently used photosensitizers, sensitized a TIC-enriched U-87MG human glioblastoma cell to radiation, and improve treatment outcome when used in combination with radiotherapy. A U-87MG tumor cell population enriched with radiation-resistant TICs becomes radio-sensitive, and an inhibition of cell proliferation and an increase in apoptosis are found in the presence of Photofrin II. Furthermore, U-87MG tumors implanted in mice treated with Photofrin II and radiation exhibit a significant reduction in angiogenesis and vasculogenesis, and an increased percentage of apoptotic TICs when compared with tumors grown in mice treated with radiation alone. Collectively, our results offer a new possible explanation for the therapeutic effects of radiosensitizing agents, and suggest that combinatorial treatment modalities can effectively prolong treatment outcome of glioblastoma tumors by inhibiting tumor growth mediated by TICs.
Topics: Animals; Apoptosis; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemoradiotherapy; Dihematoporphyrin Ether; Glioblastoma; Humans; Mice; Mice, Nude; Neoplastic Stem Cells; Neovascularization, Pathologic; Photosensitizing Agents; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 23114641
DOI: 10.4161/cbt.22630 -
World Journal of Gastroenterology Oct 2012To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC).
AIM
To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC).
METHODS
This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Forty-eight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test.
RESULTS
The PDT and control patients were comparable with respect to age, gender, health status, pre-treatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage.
CONCLUSION
Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.
Topics: Adult; Aged; Aged, 80 and over; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Endoscopy; Female; Humans; Male; Middle Aged; Photochemotherapy; Republic of Korea; Retrospective Studies; Stents
PubMed: 23112552
DOI: 10.3748/wjg.v18.i39.5589 -
Cancer Biology & Therapy Dec 2012Patients with serosal (pleural or peritoneal) spread of malignancy have few definitive treatment options and consequently have a very poor prognosis. We have previously...
Patients with serosal (pleural or peritoneal) spread of malignancy have few definitive treatment options and consequently have a very poor prognosis. We have previously shown that photodynamic therapy (PDT) can be an effective treatment for these patients, but that the therapeutic index is relatively narrow. Here, we test the hypothesis that EGFR and STAT3 activation increase survival following PDT, and that inhibiting these pathways leads to increased PDT-mediated direct cellular cytotoxicity by examining BPD-PDT in OvCa and NSCLC cells. We found that BPD-mediated PDT stimulated EGFR tyrosine phosphorylation and nuclear translocation, and that EGFR inhibition by erlotinib resulted in reduction of PDT-mediated EGFR activation and nuclear translocation. Nuclear translocation and PDT-mediated activation of EGFR were also observed in response to BPD-mediated PDT in multiple cell lines, including OvCa, NSCLC and head and neck cancer cells, and was observed to occur in response to porfimer sodium-mediated PDT. In addition, we found that PDT stimulates nuclear translocation of STAT3 and STAT3/EGFR association and that inhibiting STAT3 signaling prior to PDT leads to increased PDT cytotoxicity. Finally, we found that inhibition of EGFR signaling leads to increased PDT cytotoxicity through a mechanism that involves increased apoptotic cell death. Taken together, these results demonstrate that PDT stimulates the nuclear accumulation of both EGFR and STAT3 and that targeting these survival pathways is a potentially promising strategy that could be adapted for clinical trials of PDT for patients with serosal spread of malignancy.
Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Dihematoporphyrin Ether; ErbB Receptors; Erlotinib Hydrochloride; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Ovarian Neoplasms; Photochemotherapy; Quinazolines; RNA Interference; RNA, Small Interfering; STAT3 Transcription Factor; Signal Transduction
PubMed: 22986230
DOI: 10.4161/cbt.22256 -
Expert Review of Clinical Immunology Jul 2012Photodynamic therapy (PDT) employs the triple combination of photosensitizers, visible light and ambient oxygen. When PDT is used for cancer, it has been observed that... (Review)
Review
Photodynamic therapy (PDT) employs the triple combination of photosensitizers, visible light and ambient oxygen. When PDT is used for cancer, it has been observed that both arms of the host immune system (innate and adaptive) are activated. When PDT is used for infectious disease, however, it has been assumed that the direct antimicrobial PDT effect dominates. Murine arthritis caused by methicillin-resistant Staphylococcus aureus in the knee failed to respond to PDT with intravenously injected Photofrin(®). PDT with intra-articular Photofrin produced a biphasic dose response that killed bacteria without destroying host neutrophils. Methylene blue was the optimum photosensitizer to kill bacteria while preserving neutrophils. We used bioluminescence imaging to noninvasively monitor murine bacterial arthritis and found that PDT with intra-articular methylene blue was not only effective, but when used before infection, could protect the mice against a subsequent bacterial challenge. The data emphasize the importance of considering the host immune response in PDT for infectious disease.
Topics: Animals; Arthritis, Infectious; Dihematoporphyrin Ether; Humans; Methicillin-Resistant Staphylococcus aureus; Mice; Neutrophils; Photochemotherapy; Photosensitizing Agents; Staphylococcal Infections
PubMed: 22882222
DOI: 10.1586/eci.12.37