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The Journal of Surgical Research Dec 2014Photodynamic therapy (PDT) is a binary therapy using a drug and high-energy light source. PDT is approved for several premalignant and malignant conditions. Recent...
BACKGROUND
Photodynamic therapy (PDT) is a binary therapy using a drug and high-energy light source. PDT is approved for several premalignant and malignant conditions. Recent in-vitro and animal data suggest that enhanced tumor-specific cytotoxicity can be achieved with far less collateral damage to normal surrounding tissues if PDT is administered continuously at a lower dose rate for extended periods of time. Based on these promising preclinical data, we conducted a Phase I clinical trial of continuous low-irradiance photodynamic therapy (CLIPT) using 630 nm laser energy and intravenously administered porforin sodium as the photosensitizer. We determined the maximum tolerated dose (MTD) of CLIPT on skin and tumor response in subjects with cutaneous and subcutaneous metastatic nodules who had failed radiation and surgery.
METHODS
Patients with cutaneous and/or subcutaneous metastatic nodules that had failed radiation and surgery were offered enrollment into the trial. The initial study design planned for sequential cohorts of six subjects to be treated at increasing laser intensity, starting at 100 J/cm(2) administered continuously over 24 h (10(-2) dose rate compared with standard PDT). Dose-limiting toxicity was defined as partial or full-thickness necrosis of the surrounding tumor-free, previously irradiated skin. The MTD was defined as the highest laser energy at which ≤33% of subjects experienced the dose-limiting toxicity. Subjects received intravenous porfirmer sodium 0.8 mg/kg 48 h before commencing CLIPT. Response rates and quality of life measures were assessed.
RESULTS
Nine subjects were enrolled with chest wall progression of breast cancer following mastectomy. All had failed prior surgery and electron-beam radiation therapy. The initial two subjects were treated at 100 J/cm(2) and developed partial thickness skin necrosis. Dose reduction was therefore instituted, and the next cohort was treated at 50 J/cm(2). None of the subsequent seven subjects suffered partial or full thickness necrosis, thus establishing the MTD at 50 J/cm(2) over 24 h (0.5 mW irradiance). Six of the nine subjects (67%) had either a complete or partial clinical response. Of note, two subjects had significant regression of tumor nodules distant from the treatment field. Of the eight subjects whose terminal deoxynucleotidyl transferase dUTP nick end labeling assay results were available, 8 (100%) demonstrated histologic response to treatment as evidenced by either tumor apoptosis or regression. Quality of life measures were improved following treatment-particularly bleeding and pain from the tumor nodules.
CONCLUSIONS
The MTD of CLIPT was established at 50 J/cm(2) administered continuously over 24 h. These preliminary data suggest CLIPT may be an effective, low-morbidity therapeutic modality in the treatment of cutaneous and subcutaneous metastases of breast cancer following mastectomy. Further evaluation in a larger cohort is warranted to better assess efficacy and optimize the intervention.
Topics: Adult; Aged; Breast Neoplasms; Dihematoporphyrin Ether; Disease Progression; Dose-Response Relationship, Radiation; Female; Humans; Lasers; Mastectomy; Middle Aged; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Radiation Injuries; Skin Neoplasms; Subcutaneous Fat; Thoracic Wall
PubMed: 25043529
DOI: 10.1016/j.jss.2014.06.030 -
Photodiagnosis and Photodynamic Therapy Mar 2017The primary goal of nursing care in cases of endoscopic photodynamic therapy (PDT) for digestive tract carcinoma is to prevent phototoxicity by the intravenous...
The primary goal of nursing care in cases of endoscopic photodynamic therapy (PDT) for digestive tract carcinoma is to prevent phototoxicity by the intravenous administration of photosensitizers. The adequate protocol and management of patients should be conducted under the instruction of expert physicians. Our experiences of administering porfimer sodium and talaporfin sodium during clinical PDT provide insight regarding the specific management protocol of each photosensitizer during an in-hospital stay. We herein report our nursing protocol based on 15 years of experience. Under adequate management, PDT can be safely performed.
Topics: Cancer Care Facilities; Clinical Protocols; Dihematoporphyrin Ether; Gastrointestinal Neoplasms; Humans; Patient Education as Topic; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 28089923
DOI: 10.1016/j.pdpdt.2017.01.001 -
Photodiagnosis and Photodynamic Therapy Mar 2015To evaluate the usefulness of a novel high-resolution magnifying videoendoscope called the XG-0001 (Fujifilm, Tokyo, Japan) that is capable of PDD and PDT in... (Clinical Trial)
Clinical Trial
OBJECTIVE
To evaluate the usefulness of a novel high-resolution magnifying videoendoscope called the XG-0001 (Fujifilm, Tokyo, Japan) that is capable of PDD and PDT in experimental and clinical situations.
MATERIALS AND METHODS
The fluorescences of three photosensitizers (i.e., porfimer sodium (Photofrin), protoporphyrin IX and talaporfin sodium (Laserphyrin)) were studied experimentally via excitation with a purple diode laser (VDL, wavelength 405nm). Five consecutive patients with superficial early gastric cancer not indicated for surgery or other curative endoscopic treatment due to complicated serious diseases were enrolled in this study. After close endoscopic examinations, 2mg/kg of Photofrin were intravenously injected into the patients for PDT, and 5-aminolevulinic acid (ALA; 15-20mg/kg) was orally taken for PDD. PDD using VDL and PDT using an excimer-dye laser (630nm, 4mJ, 60Hz) were performed with the XG-0001.
RESULTS
Photofrin and Laserphyrin had experimentally the lowest and highest fluorescence intensities, respectively. The five patients comprised four men and one woman with a mean age 75.2 year and an age range of 56-83 years. Two additional cancerous lesions were newly detected by magnifying pharmacoendoscopy. In each patient, PDD was successfully performed. PDT could also safely performed and CR was obtained in 71.4% (5/7) of the cancerous lesions in five patients, and no serious complications were encountered.
CONCLUSION
The XG-0001, which is based on a simultaneous videoendoscopy method that uses an RGB color chip CCD, proved extremely useful in routine use and also in PDD and PDT for gastric cancer.
Topics: Aged; Aged, 80 and over; Endoscopes, Gastrointestinal; Equipment Design; Equipment Failure Analysis; Female; Humans; Image Enhancement; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Stomach Neoplasms; Treatment Outcome; Video Recording
PubMed: 25462577
DOI: 10.1016/j.pdpdt.2014.10.010 -
Journal of Photochemistry and... Jan 2018The inhibitor of DNA binding and cell differentiation (Id) proteins are dominant negative regulators of the helix-loop-helix transcription factor family and play a key...
The inhibitor of DNA binding and cell differentiation (Id) proteins are dominant negative regulators of the helix-loop-helix transcription factor family and play a key role during development as well as in vascular disorders and cancer. In fact, impairing the Id-protein activity in cancer cells reduces cell growth and even chemoresistance. Recently, we have shown that a synthetic Id-protein ligand (1Y) consisting of a cyclic nonapeptide can reduce the viability of the two breast cancer cell lines MCF-7 and T47D and of the bladder cancer cells T24 to about 50% at concentrations ≥100μM. Moreover, the cyclopeptide displays both proapoptotic and antiproliferative effects on MCF-7 cells. Herein, we show that the cyclopeptide does not induce cell death at the dose of 5μΜ, but it still inhibits MCF-7 and T24 cell proliferation, which correlates with an increased protein level of the cell-cycle regulator p27. Furthermore, 1Y-pretreated MCF-7, T47D, and T24 cells are more susceptible than untreated cells to the phototoxic effects of the three photosensitizers meta-tetra(hydroxyphenyl)chlorin, porfimer sodium, and hypericin, which are applied in photodynamic therapy (PDT). The combination of the Id-protein ligand with each of the light-activated photosensitizers shows synergistic effects on the reduction of cell viability. In conclusion, an Id-protein ligand with moderate cancer cell killing activity at concentrations ≥100μM can be applied at a 20-fold lower and barely toxic dose to raise the sensitivity of cancer cells towards phototoxicity associated with photodynamic treatment. This suggests the potential benefit of targeting the Id proteins in combined drug approaches for cancer therapy.
Topics: Anthracenes; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cyclin-Dependent Kinase Inhibitor p27; Dihematoporphyrin Ether; Drug Synergism; Humans; Inhibitor of Differentiation Protein 1; Light; MCF-7 Cells; Nanostructures; Peptides, Cyclic; Perylene; Photosensitizing Agents; Porphyrins
PubMed: 29245122
DOI: 10.1016/j.jphotobiol.2017.11.038 -
Photochemistry and Photobiology Jan 2019Malignant pleural mesothelioma remains difficult to treat, with high failure rates despite optimal therapy. We present a novel prospective trial combining proton therapy...
A Novel Prospective Study Assessing the Combination of Photodynamic Therapy and Proton Radiation Therapy: Safety and Outcomes When Treating Malignant Pleural Mesothelioma.
Malignant pleural mesothelioma remains difficult to treat, with high failure rates despite optimal therapy. We present a novel prospective trial combining proton therapy (PT) and photodynamic therapy (PDT) and the largest-ever mesothelioma PT experience (n = 10). PDT photosensitizers included porfimer sodium (2 mg·kg ; 24 h drug-light interval) or 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) (4 mg·m ;48 h) with wavelengths of 630 nm to 60J·cm and 665 nm to 15-45J·cm , respectively. With a median age of 69 years, patients were predominantly male (90%) with epithelioid histology (100%) and stage III-IV disease (100%). PT was delivered to a median of 55.0 CGE/1.8-2.0 CGE (range 50-75 CGE) adjuvantly (n = 8) or as salvage therapy (n = 2) following extended pleurectomy/decortication (ePD)/PDT. Two-year local control was 90%, with distant and regional failure rates of 50% and 30%, respectively. All patients received chemotherapy, and four received immunotherapy. Surgical complications included atrial fibrillation (n = 3), pneumonia (n = 2), and deep vein thrombosis (n = 2). Median survival from PT completion was 19.5 months (30.3 months from diagnosis), and 1- and 2-year survival rates were 58% and 29%. No patient experienced CTCAEv4 grade ≥2 acute or late toxicity. Our prolonged survival in very advanced-stage patients compares favorably to survival for PT without PDT and photon therapy with PDT, suggesting possible spatial or systemic cooperativity and immune effect.
Topics: Aged; Aged, 80 and over; Combined Modality Therapy; Female; Humans; Male; Mesothelioma; Middle Aged; Photochemotherapy; Photosensitizing Agents; Pleural Neoplasms; Prospective Studies; Proton Therapy; Treatment Outcome
PubMed: 30485442
DOI: 10.1111/php.13065 -
Photodiagnosis and Photodynamic Therapy Mar 2018To assess the effect of photodynamic therapy (PDT) with talaporfin sodium, a second-generation photosensitizer, on oral squamous cell carcinoma (SCC).
OBJECTIVE
To assess the effect of photodynamic therapy (PDT) with talaporfin sodium, a second-generation photosensitizer, on oral squamous cell carcinoma (SCC).
METHODS
Eight patients who were diagnosed with oral SCC without any metastasis and underwent talaporfin sodium-mediated PDT (t-PDT) were included in this study. Biopsies were performed 4-6 weeks after t-PDT. The clinical response was evaluated using Response Evaluation Criteria in Solid Tumors.
RESULTS
Complete response (CR) was achieved in six of eight cases, and two cases showed partial response (PR) as a clinical outcome of t-PDT. Recurrence occurred in one of the CR cases 9 months after irradiation. The patient underwent tumor resection and no recurrence was found after surgery. The two cases with PR died from the cancer despite additional PDT.
CONCLUSION
t-PDT is an effective treatment strategy for oral SCC. Talaporfin sodium has an advantage with regard to early elimination from the body compared with porfimer sodium.
Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Lasers, Semiconductor; Male; Middle Aged; Mouth Neoplasms; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Porphyrins
PubMed: 29198764
DOI: 10.1016/j.pdpdt.2017.11.016 -
Photodiagnosis and Photodynamic Therapy Mar 2016Dental implants are commonly used today for the treatment of partially and fully edentulous patients. Despite the high success rate they are not resistant to...
BACKGROUND
Dental implants are commonly used today for the treatment of partially and fully edentulous patients. Despite the high success rate they are not resistant to complications and failure due to a variety of problems including peri-implantitis or peri-mucositis due to bacterial biofilm formation on the implant surface. The use of non-surgical and surgical treatment procedure to promote healing in cases with peri-implantitis have limited efficacy. Here we studied the ability of photodynamic therapy to destroy a known bacterial pathogen and the extracellular matrix architecture of biofilm attached to titanium plates and germanium prisms.
METHODS
Titanium plates or germanium prisms were incubated for 24h with Fusobacterium nucleatum a fusiform, gram-negative bacterium was used to enable biofilm formation. Photodynamic therapy was carried out by incubating the biofilm samples on each substrata with porfimer sodium. Treatment was carried out using a diode laser at 630nm, 150mW/cm(2) for light doses ranging from 25-100J/cm(2). Evaluation of killing efficacy was done by counting colony forming units compared to controls. Multiple attenuated internal reflection-infrared spectroscopy (MAIR-IR) and SEM were used to analyze the samples pre and post PDT for validation.
RESULTS
F. nucleatum was significantly reduced in a dose dependent manner by treatment with PDT. Changes in biofilm components and strength of bioadhesion were examined with MAIR-IR following jet impingement using calibrated water jets. SEM demonstrates significant morphological alterations in the bacteria, consistent with damage associated with exposure to reactive oxygen species.
CONCLUSION
The results are indicative that aPDT is a method that can be used to eradicate micro-organisms associated with biofilm in peri-implantitis on relevant substrata. Data shows that the slime layer of the biofilm is removed and that further methods need to be employed to completely remove weakened or destroyed biofilm matrix components. Reactive oxygen species (ROS) mediated oxidative damage results in morphologic changes as a consequence of changes in cell membrane integrity.
Topics: Biofilms; Dental Implants; Dihematoporphyrin Ether; Extracellular Matrix; Fusobacteria; Photochemotherapy; Photosensitizing Agents; Sterilization
PubMed: 26617192
DOI: 10.1016/j.pdpdt.2015.11.007 -
International Journal of Molecular... Jun 2023Current treatment for prostate cancer is dependent on the stages of the cancer, recurrence, and genetic factors. Treatment varies from active surveillance or watchful...
Current treatment for prostate cancer is dependent on the stages of the cancer, recurrence, and genetic factors. Treatment varies from active surveillance or watchful waiting to prostatectomy, chemotherapy, and radiation therapy in combination or alone. Although radical prostate cancer therapy reduces the advancement of the disease and its mortality, the increased disease treatment associated morbidity, erectile dysfunction, and incontinence affect the quality of life of cancer survivors. To overcome these problems, photodynamic therapy (PDT) has previously been investigated using Photofrin as a photosensitizer (PS). However, Photofrin-PDT has shown limitations in treating prostate cancer due to its limited tumor-specificity and the depth of light penetration at 630 nm (the longest wavelength absorption of Photofrin). The results presented herein show that this limitation can be solved by using a near infrared (NIR) compound as a photosensitizer (PS) for PDT and the same agent also acts as a sonosensitizer for SDT (using ultrasound to activate the compound). Compared to light, ultrasound has a stronger penetration ability in biological tissues. Exposing the PS (or sonosensitizer) to ultrasound (US) initiates an electron-transfer process with a biological substrate to form radicals and radical ions (type I reaction). In contrast, exposure of the PS to light (PDT) generates singlet oxygen (type II reaction). Therefore, the reactive oxygen species (ROS) produced by SDT and PDT follow two distinct pathways, i.e., type I (oxygen independent) and type II (oxygen dependent), respectively, and results in significantly enhanced destruction of tumor cells. The preliminary in vitro and in vivo results in a PC3 cell line and tumor model indicate that the tumor specificality of the therapeutic agent(s) can be increased by targeting galectin-1 and galectin-3, known for their overexpression in prostate cancer.
Topics: Male; Humans; Mice; Animals; Photosensitizing Agents; Photochemotherapy; Dihematoporphyrin Ether; Quality of Life; Prostatic Neoplasms; Oxygen; Cell Line, Tumor
PubMed: 37445799
DOI: 10.3390/ijms241310624 -
Journal of Thoracic Oncology : Official... Feb 2016We report a phase I trial of photodynamic therapy (PDT) of carcinoma in situ (CIS) and microinvasive cancer (MIC) of the central airways with the photosensitizer (PS)...
A Phase I Study of Light Dose for Photodynamic Therapy Using 2-[1-Hexyloxyethyl]-2 Devinyl Pyropheophorbide-a for the Treatment of Non-Small Cell Carcinoma In Situ or Non-Small Cell Microinvasive Bronchogenic Carcinoma: A Dose Ranging Study.
INTRODUCTION
We report a phase I trial of photodynamic therapy (PDT) of carcinoma in situ (CIS) and microinvasive cancer (MIC) of the central airways with the photosensitizer (PS) 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH). HPPH has the advantage of minimal general phototoxicity over the commonly used photosensitizer porfimer sodium (Photofrin; Pinnacle Biologics, Chicago, IL).
METHODS
The objectives of this study were (1) to determine the maximally tolerated light dose at a fixed photosensitizer dose and (2) to gain initial insight into the effectiveness of this treatment approach. Seventeen patients with 21 CIS/MIC lesions were treated with HPPH with light dose escalation starting from 75 J/cm2 and increasing to 85, 95,125, and 150 J/cm2 respectively. Follow-up bronchoscopy for response assessment was performed at 1 and 6 months, respectively.
RESULTS
The rate of pathological complete response (CR) was 82.4% (14 of 17 evaluable lesions; 14 patients) at 1 month and 72.7% (8/11 evaluable lesions; 8 patients) at 6 months. Only four patients developed mild skin erythema. One of the three patients in the 150 J/cm2 light dose group experienced a serious adverse event. This patient had respiratory distress caused by mucus plugging, which precipitated cardiac ischemia. Two additional patients treated subsequently at this light dose had no adverse events. The sixth patient in this dose group was not recruited and the study was terminated because of delays in HPPH supply. However, given the observed serious adverse event, it is recommended that the light dose does not exceed 125 J/cm2.
CONCLUSIONS
PDT with HPPH can be safely used for the treatment of CIS/MIC of the airways, with potential effectiveness comparable to that reported for porfimer sodium in earlier studies.
Topics: Aged; Aged, 80 and over; Carcinoma in Situ; Carcinoma, Bronchogenic; Carcinoma, Non-Small-Cell Lung; Chlorophyll; Dose-Response Relationship, Drug; Female; Humans; Lung Neoplasms; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents
PubMed: 26718878
DOI: 10.1016/j.jtho.2015.10.020 -
Cellular Physiology and Biochemistry :... 2015Photodynamic therapy (PDT) is a promising noninvasive technique, which has been successfully applied to the treatment of human cancers. Studies have shown that the Bcl-2...
BACKGROUND/AIMS
Photodynamic therapy (PDT) is a promising noninvasive technique, which has been successfully applied to the treatment of human cancers. Studies have shown that the Bcl-2 family proteins play important roles in PDT-induced apoptosis. However, whether Bcl-2-interacting mediator of cell death (Bim) is involved in photodynamic treatment remains unknown. In this study, we attempt to determine the effect of Bim on Photofrin photodynamic treatment (PPT)-induced apoptosis in human lung adenocarcinoma ASTC-a-1 cells.
METHODS
The translocation of Bim/Bax of the cells were monitored by laser confocal scanning microscope. The levels of Bim protein and activated caspase-3 in cells were detected by western blot assay. Caspase-3 activities were measured by Caspase-3 Fluorogenic Substrate (Ac-DEVD-AFC) analysis. The induction of apoptosis was detected by Hoechst 33258 and PI staining as well as flow cytometry analysis. The effect of Bim on PPT-induced apoptosis was determined by RNAi.
RESULTS
BimL translocated to mitochondria in response to PPT, similar to the downstream pro-apoptotic protein Bax activation. PPT increased the level of Bim and activated caspase-3 in cells and that knockdown of Bim by RNAi significantly protected against caspase-3 activity. PPT-induced apoptosis were suppressed in cells transfected with shRNA-Bim.
CONCLUSION
We demonstrated the involvement of Bim in PPT-induced apoptosis in human ASTC-a-1 lung adenocarcinoma cells and suggested that enhancing Bim activity might be a potential strategy for treating human cancers.
Topics: Apoptosis; Apoptosis Regulatory Proteins; Bcl-2-Like Protein 11; Blotting, Western; Caspase 3; Cell Line, Tumor; Dihematoporphyrin Ether; Humans; Lasers; Membrane Proteins; Microscopy, Electron, Scanning; Mitochondria; Photochemotherapy; Photosensitizing Agents; Proto-Oncogene Proteins; RNA Interference; RNA, Small Interfering; bcl-2-Associated X Protein
PubMed: 25791936
DOI: 10.1159/000373968