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Photodiagnosis and Photodynamic Therapy Dec 2022Photodynamic therapy involves using a photosensitizer with l illumination and is recommended for treating early, centrally located lung cancers, but it is not a standard...
BACKGROUND
Photodynamic therapy involves using a photosensitizer with l illumination and is recommended for treating early, centrally located lung cancers, but it is not a standard treatment for peripheral lung tumor.. We previously proposed a novel light delivery method, in which lipiodol is perfused into the bronchial tree to increase the scope of illumination via the fiber effect. Herein, we attempted this novel technique under electromagnetic bronchoscope guidance in a hybrid operation room where lipiodol facilitated light diffusion, and evaluated the effectiveness and feasibility of this technique for peripheral lung cancers.
METHODS
This phase 0 pilot study included three patients with peripheral lung cancers (primary tumors ≤20-mm diameter). The photodynamic therapy was administered using Porfimer sodium as the photosensitizer, and an electromagnetic navigation bronchoscope in a hybrid operating room to guide the catheter to the tumor. This facilitated lipiodol infusion to encase the tumor and permit the transbronchial photodynamic therapy ablation.
RESULTS
Administering 630 nm 200 J/cm (400mW/500sec) energy through a 3-cm cylindrical diffusing laser fiber was safe; no significant acute complications were observed. Although the treatment outcome was unsatisfactory due to the low light dose, tumor pathology in one case revealed tumor necrosis, with no significant damage to the surrounding lung tissue.
CONCLUSIONS
Novel light delivery transbronchial photodynamic therapy ablation for peripheral lung tumors is feasible and safe. Additional clinical trials may help determine the best illumination plan and light dose through multiple deliveries from multiple angles.
Topics: Humans; Photochemotherapy; Pilot Projects; Dihematoporphyrin Ether; Photosensitizing Agents; Lung Neoplasms
PubMed: 35963527
DOI: 10.1016/j.pdpdt.2022.103063 -
Photodiagnosis and Photodynamic Therapy Sep 2022Photodynamic therapy (PDT) is an FDA approved treatment for lung cancer. In the United States the photosensitizer porfimer sodium (Photofrin®, Pinnacle Biologics) is...
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.
Topics: Aged; Dihematoporphyrin Ether; Humans; Lung; Lung Neoplasms; Male; Photochemotherapy; Photosensitizing Agents
PubMed: 35803556
DOI: 10.1016/j.pdpdt.2022.103001 -
Methods in Molecular Biology (Clifton,... 2022Photofrin-based photodynamic therapy (PDT) is approved for clinical use by the US Food and Drug Administration and the European Medicines Agency and is among the most...
Photofrin-based photodynamic therapy (PDT) is approved for clinical use by the US Food and Drug Administration and the European Medicines Agency and is among the most widely used photosensitizer for the treatment of cancer. It was broadly reported that both the innate and the adaptive arms of immune response can be activated by PDT and play a critical role in the anticancer outcome of this treatment. PDT leads to the induction of acute local inflammation that includes leukocyte infiltration as well as increased activation and production of pro-inflammatory factors and cytokines. These events can lead to the development of systemic and specific antitumor immune response. Combining Photofrin-PDT with the epigenetic agent 5-aza-2'-deoxycytidine results in potentiated antitumor effects in vivo. Understanding the molecular mechanisms underlying this phenomenon would be invaluable for clinical development of this therapeutic approach. This chapter describes a detailed protocol allowing evaluation of specific antitumor immune response induced by PDT.
Topics: Decitabine; Dihematoporphyrin Ether; Epigenesis, Genetic; Immunity; Photochemotherapy; United States
PubMed: 35505032
DOI: 10.1007/978-1-0716-2099-1_27 -
Photodiagnosis and Photodynamic Therapy Jun 2022Photodynamic therapy (PDT) is an internationally approved ablation technique for endo-bronchial lung cancer. The majority of reported outcomes are for central and...
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.
Topics: Bronchoscopy; Carcinoma, Non-Small-Cell Lung; Dihematoporphyrin Ether; Humans; Lung Neoplasms; Photochemotherapy
PubMed: 35331954
DOI: 10.1016/j.pdpdt.2022.102825 -
Bioengineering (Basel, Switzerland) Feb 2022The effectiveness of photodynamic therapy (PDT) is based on the triad effects of photosensitizer (PS), molecular oxygen and visible light on malignant tumors. Such... (Review)
Review
The effectiveness of photodynamic therapy (PDT) is based on the triad effects of photosensitizer (PS), molecular oxygen and visible light on malignant tumors. Such complex induces a multifactorial manner including reactive-oxygen-species-mediated damage and the killing of cells, vasculature damage of the tumor, and activation of the organism immunity. The effectiveness of PDT depends on the properties of photosensitizing drugs, their selectivity, enhanced photoproduction of reactive particles, absorption in the near infrared spectrum, and drug delivery strategies. Photosensitizers of the tetrapyrrole structure (porphyrins) are widely used in PDT because of their unique diagnostic and therapeutic functions. Nevertheless, the clinical use of the first-generation PS (sodium porfimer and hematoporphyrins) revealed difficulties, such as long-term skin photosensitivity, insufficient penetration into deep-seated tumors and incorrect localization to it. The second generation is based on different approaches of the synthesis and conjugation of porphyrin PS with biomolecules, which made it possible to approach the targeted PDT of tumors. Despite the fact that the development of the second-generation PS started about 30 years ago, these technologies are still in demand and are in intensive development, especially in the direction of improving the process of optimization split linkers responsive to input. Bioconjugation and encapsulation by targeting molecules are among the main strategies for developing of the PS synthesis. A targeted drug delivery system with the effect of increased permeability and retention by tumor cells is one of the ultimate goals of the synthesis of second-generation PS. This review presents porphyrin PS of various generations, discusses factors affecting cellular biodistribution and uptake, and indicates their role as diagnostic and therapeutic (theranostic) agents. New complexes based on porphyrin PS for photoimmunotherapy are presented, where specific antibodies are used that are chemically bound to PS, absorbing light from the near infrared part of the spectrum. Additionally, a two-photon photodynamic approach using third-generation photosensitizers for the treatment of tumors is discussed, which indicates the prospects for the further development of a promising method antitumor PDT.
PubMed: 35200435
DOI: 10.3390/bioengineering9020082 -
Frontiers in Oncology 2021Blood vessels in the brain tissue form a compact vessel structure and play an essential role in maintaining the homeostasis of the neurovascular system. The low dosage...
Blood vessels in the brain tissue form a compact vessel structure and play an essential role in maintaining the homeostasis of the neurovascular system. The low dosage of photodynamic intervention (PDT) significantly affects the expression of cellular biomarkers. To understand the impact of photodynamic interventions on cerebrovascular endothelial cells, we evaluated the dosage-dependent impact of porfimer sodium-mediated PDT on B.END3 cells using flow cytometer, comet assay, RNA sequencing, and bioinformatics analysis. To examine whether PDT can induce disorder of intracellular organelles, we did not observe any significance damage of DNA and cellular skeleton. Moreover, expression levels of cellular transporters-related genes were significantly altered, implying the drawbacks of PDT on cerebrovascular functions. To address the potential molecular mechanisms of these phenotypes, RNA sequencing and bioinformatics analysis were employed to identify critical genes and pathways among these processes. The gene ontology (GO) analysis and protein-protein interaction (PPI) identified 15 hub genes, highly associated with cellular mitosis process (, , , , , , , , , ) and DNA replication (, , , ). Gene set enrichment analysis (GSEA) reveals that and pathways may play a critical role in regulating expression levels of transporter-related genes. To further perform qRT-PCR assays, we find that and pathways were substantially up-regulated, consistent with GSEA analysis. The current findings suggested that a low dosage of PDT intervention may be detrimental to the homeostasis of blood-brain barrier (BBB) by inducing the inflammatory response and affecting the expression of surface biomarkers.
PubMed: 34881175
DOI: 10.3389/fonc.2021.731414 -
Photodiagnosis and Photodynamic Therapy Mar 2022To assess the influence of different photosensitizers activated by PDT as a disinfectant in comparison to conventional sodium hypochlorite (NaOCl) on the EBS (extrusion...
AIM
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.
METHODS
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.
RESULTS
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).
CONCLUSION
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.
Topics: Curcumin; Dental Pulp Cavity; Dentin; Dihematoporphyrin Ether; Disinfection; Edetic Acid; Humans; Materials Testing; Photochemotherapy; Riboflavin; Root Canal Irrigants; Root Canal Preparation; Rose Bengal; Sodium Hypochlorite
PubMed: 34781034
DOI: 10.1016/j.pdpdt.2021.102625 -
Esophagus : Official Journal of the... Oct 2021Talaporfin sodium photodynamic therapy (tPDT) is an effective salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Repeated tPDT could also...
BACKGROUND
Talaporfin sodium photodynamic therapy (tPDT) is an effective salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Repeated tPDT could also be indicated for local recurrence or residue after the first salvage tPDT. However, the safety and efficacy of repeated tPDT have not been elucidated.
METHODS
We reviewed 52 patients with esophageal cancer who were treated with the first tPDT at Kyoto University Hospital between October 2015 and April 2020.
RESULTS
Among 52 patients, repeated tPDT after the first tPDT was indicated for 13 patients (25%), of which six had residual tumor, four had local recurrence after complete response (CR) after the first tPDT at the primary site, and six had metachronous lesion. The total session of repeated tPDT was 25; 16 were for primary sites and nine were for metachronous sites. Among them, six patients (46.2%) achieved local (L)-CR and nine lesions (56.3%) achieved lesion L-CR. By session, 10 sessions (40%) achieved L-CR. There were no severe adverse events except for one patient; this patient showed grade 3 esophageal stenosis and perforation after the third tPDT on the same lesion that was previously treated with porfimer sodium photodynamic therapy four times.
CONCLUSION
Repeated tPDT could be an effective and safe treatment for local failure even after salvage tPDT for esophageal cancer.
Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Neoplasm Recurrence, Local; Photochemotherapy; Porphyrins
PubMed: 34106353
DOI: 10.1007/s10388-021-00853-x -
The Journal of Surgical Research Jul 2021Lung cancer is the greatest cause of cancer mortality in the United States, necessitating ongoing improvements in current treatment techniques. Photodynamic therapy... (Comparative Study)
Comparative Study
BACKGROUND
Lung cancer is the greatest cause of cancer mortality in the United States, necessitating ongoing improvements in current treatment techniques. Photodynamic therapy (PDT) involves the interaction between a photosensitizer, light, and oxygen. The resulting release of reactive oxygen species causes tumor necrosis. It has been used as an endoscopic technique for the palliation of lung cancer. Porfimer sodium (Photofrin) is the only Food and Drug Administration-approved photosensitizer for PDT but has limited depth of penetration and produces prolonged skin phototoxicity. Multiple newer photosensitizers are in development, including PS785. The effectiveness of PS785 was compared with porfimer sodium in the treatment of human lung cancer xenografts in mice.
METHODS
Human non-small cell lung cancer (NSCLC) xenografts were established in severe combined immunodeficient mice and grouped into small (3-5 mm) and large tumors (6-10 mm). PS785 or porfimer sodium was administered intravenously, and PDT was executed at 24, 48, or 72 h after injection. The primary endpoint was the delay of tumor regrowth after PDT.
RESULTS
Porfimer sodium and PS785 produced statistically similar delays of tumor regrowth after PDT when small tumors were treated at 24 and 48 h. At 72 h, PS785 performed better in small tumors. However, for large tumors, PS785 produced no delay in tumor regrowth at any time point.
CONCLUSIONS
PS785 and porfimer sodium were able to effectively treat NSCLC to a depth of ≤5 mm. However, porfimer sodium was more effective in treating NSCLC tumors to a depth of 6-10 mm. Further efforts are required to produce photosensitizers that will facilitate PDT of larger tumors.
Topics: Animals; Carcinoma, Non-Small-Cell Lung; Dihematoporphyrin Ether; Humans; Injections, Intravenous; Lung; Lung Neoplasms; Mice; Photochemotherapy; Photosensitizing Agents; Pneumonectomy; Xenograft Model Antitumor Assays
PubMed: 33713956
DOI: 10.1016/j.jss.2020.12.067 -
Photodiagnosis and Photodynamic Therapy Sep 2020Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma that arises in areas rich in apocrine sweat glands. Photodynamic therapy (PDT) is a... (Review)
Review
BACKGROUND
Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma that arises in areas rich in apocrine sweat glands. Photodynamic therapy (PDT) is a non-invasive technique demonstrating clinical efficacy in various case reports and case series for the treatment of EMPD.
METHODS
A review of the current literature of patients with EMPD treated with PDT.
RESULTS
177 patients with 211 lesions were included in this review with an overall complete response rate of 59.7 %. Lesion size was correlated with the efficacy of 5-aminolevulinic acid (ALA) PDT. Topical methyl-ALA had lower complete response rates compared to ALA. Systemic PDT with intravenous sodium porfimer had high response rates but can be associated with more adverse reactions. The efficacy of PDT was enhanced with the combination of other treatments such as surgery, imiquimod, or laser ablation. PDT was also shown to be effective for previously treated lesions, recurrent lesions, and select invasive lesions.
CONCLUSION
PDT can be a therapeutic option for EMPD patients. Given the lack of PDT guidelines, general recommendations for treatment are offered.
Topics: Aminolevulinic Acid; Dihematoporphyrin Ether; Humans; Paget Disease, Extramammary; Photochemotherapy; Photosensitizing Agents
PubMed: 32645437
DOI: 10.1016/j.pdpdt.2020.101911