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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 -
The Journal of Surgical Research Jan 2016There is a need to develop novel therapies for non-small cell lung cancer (NSCLC). Photodynamic therapy has been used successfully for endobronchial palliation of NSCLC,... (Comparative Study)
Comparative Study
BACKGROUND
There is a need to develop novel therapies for non-small cell lung cancer (NSCLC). Photodynamic therapy has been used successfully for endobronchial palliation of NSCLC, and its role in early stages of disease is being explored. We hypothesized that a novel photosensitizer, PS1, would be more effective than the standard agent, porfimer sodium (Photofrin or PFII), in treating human lung cancer xenografts in mice.
MATERIALS AND METHODS
Patient-derived NSCLC xenografts were established subcutaneously in severe combined immune deficiency mice. Two groups of five mice were injected with PS1 (3-[1'-m-iodobenzyloxy]ethyl-3-devinylpyropheophorbide-a), a chlorophyll-a derivative, or PFII (a purified version of hematoporphyrin derivative) and then treated with nonthermal laser light. Four mice were treated with laser light without photosensitizer and six mice received no treatment at all. All mice were then observed for tumor growth. The tumor growth end point, time-to-1000 mm(3), was evaluated using standard Kaplan-Meier methods and the log-rank test. Tumor hematoxylin and eosin and caspase 3 staining was done to evaluate necrosis and apoptosis.
RESULTS
The median time-to-1000 mm(3) was 12, 12, 26, and 52 d for the control, light only, PFII, and PS1 groups. There was a significant association between the tumor growth end point and treatment (P < 0.05). Hematoxylin and eosin staining revealed <1%, 0%, 67%, and 80% necrosis, and caspase 3 positivity was 2%, <1%, 17%, and 39%, respectively, in the same four groups.
CONCLUSIONS
The mice treated with PS1 exhibited a longer time for tumor regrowth and showed more tumor necrosis and apoptosis compared with the other treatment groups. Thus, the novel photosensitizer, PS1, was demonstrated to be more effective than porfimer sodium in this preclinical pilot study.
Topics: Animals; Carcinoma, Non-Small-Cell Lung; Chlorophyll; Dihematoporphyrin Ether; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Mice; Mice, SCID; Neoplasm Transplantation; Photochemotherapy; Photosensitizing Agents; Pilot Projects; Transplantation, Heterologous; Treatment Outcome
PubMed: 26494011
DOI: 10.1016/j.jss.2015.07.024 -
Journal of Bronchology & Interventional... Apr 2023Newer navigational bronchoscopy technologies render peripheral lung lesions accessible for biopsy and potential treatment. We investigated whether photodynamic therapy...
BACKGROUND
Newer navigational bronchoscopy technologies render peripheral lung lesions accessible for biopsy and potential treatment. We investigated whether photodynamic therapy (PDT) delivered via navigational bronchoscopy is feasible and safe for ablation of peripheral lung tumors.
METHODS
Two studies evaluated PDT in patients with solid peripheral lung tumors followed by clinical follow-up (nonresection study, N=5) or lobectomy (resection study, N=10). Porfimer sodium injection was administered 40 to 50 hours before navigational bronchoscopy. Lesion location was confirmed by radial probe endobronchial ultrasonography. An optical fiber diffuser was placed within or adjacent to the tumor under fluoroscopic guidance; laser light (630 nm wavelength) was applied at 200 J/cm of diffuser length for 500 seconds. Tumor response was assessed by modified Response Evaluation Criteria in Solid Tumors at 3 and 6 months postprocedure (nonresection study) and pathologically (resection study).
RESULTS
There were no deaths, discontinuations for adverse events, or serious or grade ≥3 adverse events related to study treatments. Photosensitivity reactions occurred in 8 of 15 patients: 6 mild, 1 moderate, 1 severe (elevated porphyrins noted in blood after treatment). Among 5 patients with clinical follow-up, 1 had complete response, 3 had stable disease, and 1 had progressive disease at 6 months follow-up. Among 10 patients who underwent lobectomy, 1 had no evidence of tumor at resection (complete response), 3 had 40% to 50% tumor cell necrosis, 2 had 20% to 35%, and 4 had 5% to 10%.
CONCLUSION
PDT for nonthermal ablation of peripheral lung tumors was feasible and safe in this small study. Further study is warranted to evaluate efficacy and corroborate the safety profile.
Topics: Humans; Photochemotherapy; Feasibility Studies; Dihematoporphyrin Ether; Lung Neoplasms; Light; Photosensitizing Agents
PubMed: 35968968
DOI: 10.1097/LBR.0000000000000889 -
Molecules (Basel, Switzerland) Jan 2017Photodynamic therapy (PDT) investigations have seen stable increases and the development of new photosensitizers is a heated topic. Sinoporphyrin sodium is a new...
Photodynamic therapy (PDT) investigations have seen stable increases and the development of new photosensitizers is a heated topic. Sinoporphyrin sodium is a new photosensitizer isolated from Photofrin. This article evaluated its anticancer effects by clonogenic assays, MTT assays and xenograft experiments in comparison to Photofrin. The clonogenicity inhibition rates of sinoporphyrin sodium-PDT towards four human cancer cell lines ranged from 85.5% to 94.2% at 0.5 μg/mL under 630 nm irradiation of 30 mW/cm² for 180 s. For MTT assays, the IC ranges of Photofrin-PDT and sinoporphyrin sodium-PDT towards human cancer cells were 0.3 μg/mL to 5.5 μg/mL and 0.1 μg/mL to 0.8 μg/mL under the same irradiation conditions, respectively. The IC values of Photofrin-PDT and sinoporphyrin sodium-PDT towards human skin cells, HaCaT, were 10 μg/mL and 1.0 μg/mL, respectively. Esophagus carcinoma and hepatoma xenograft models were established to evaluate the in vivo antineoplastic efficacy. A control group, Photofrin-PDT group (20 mg/kg) and sinoporphyrin sodium group at three doses, 0.5 mg/kg, 1 mg/kg and 2 mg/kg, were set. Mice were injected with photosensitizers 24 h before 60 J 630 nm laser irradiation. The tumor weight inhibition ratio of 2 mg/kg sinoporphyrin sodium-PDT reached approximately 90%. Besides, the tumor growths were significantly slowed down by 2 mg/kg sinoporphyrin sodium-PDT, which was equivalent to 20 mg/kg Photofrin-PDT. In sum, sinoporphyrin sodium-PDT showed great anticancer efficacy and with a smaller dose compared with Photofrin. Further investigations are warranted.
Topics: Animals; Antineoplastic Agents; Cell Line, Transformed; Cell Line, Tumor; Dihematoporphyrin Ether; Drug Evaluation, Preclinical; Esophageal Neoplasms; Female; Humans; Inhibitory Concentration 50; Keratinocytes; Lasers, Excimer; Light; Liver Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Photochemotherapy; Photosensitizing Agents; Porphyrins; Tumor Burden; Xenograft Model Antitumor Assays
PubMed: 28085075
DOI: 10.3390/molecules22010112 -
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 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 -
Life Sciences Feb 2023Photodynamic therapy (PDT) is a treatment modality for several cancers involving the administration of a tumour-localising photosensitiser (PS) and its subsequent...
AIMS
Photodynamic therapy (PDT) is a treatment modality for several cancers involving the administration of a tumour-localising photosensitiser (PS) and its subsequent activation by light, resulting in tumour damage. Ras oncogenes have been strongly associated with chemo- and radio-resistance. Based on the described roles of adhesion and cell morphology on drug resistance, we studied if the differences in shape, cell-extracellular matrix and cell-cell adhesion induced by Ras transfection, play a role in the resistance to PDT.
MATERIALS AND METHODS
We employed the human normal breast HB4a cells transfected with H-RAS and a panel of five PSs.
KEY FINDINGS
We found that resistance to PDT of the HB4a-Ras cells employing all the PSs, increased between 1.3 and 2.5-fold as compared to the parental cells. There was no correlation between resistance and intracellular PS levels or PS intracellular localisation. Even when Ras-transfected cells present lower adherence to the ECM proteins, this does not make them more sensitive to PDT or chemotherapy. On the contrary, a marked gain of resistance to PDT was observed in floating cells as compared to adhesive cells, accounting for the higher ability conferred by Ras to survive in conditions of decreased cell-extracellular matrix interactions. HB4a-Ras cells displayed disorganisation of actin fibres, mislocalised E-cadherin and vinculin and lower expression of E-cadherin and β1-integrin as compared to HB4a cells.
SIGNIFICANCE
Knowledge of the mechanisms of resistance to photodamage in Ras-overexpressing cells may lead to the optimization of the combination of PDT with other treatments.
Topics: Humans; Female; Cell Adhesion; Genes, ras; Breast Neoplasms; Photosensitizing Agents; Cadherins; Photochemotherapy
PubMed: 36526044
DOI: 10.1016/j.lfs.2022.121287 -
Laser Therapy Sep 2014In Japan the rise in the average life expectancy has caused an increase in the proportion of the population who are classed as geriatric. Accordingly, the number of...
BACKGROUND AND AIMS
In Japan the rise in the average life expectancy has caused an increase in the proportion of the population who are classed as geriatric. Accordingly, the number of elderly people being treated for cancer is increasing concomitantly. However, with the increase in age, the numbers of prior complications also increase. This is especially so in the advanced-aged patients, defined in Japan as those over the age of 85. Such complications may be too high risk for radical surgery and a less invasive treatment is warranted. Photodynamic therapy (PDT) is a noninvasive treatment approved by the Japanese National Health Insurance for the treatment of early stage superficial type esophageal and gastric cancers, early stage uterine cervical cancers and dysplasia, and early and advanced lung cancer. We report herein on the efficacy of palliative PDT using talaporfin sodium (Laserphyrin(®)) for a case of inoperable gastric cancer.
MATERIAL AND METHODS
The patient was an 87-year-old-man, a diabetic with histories of diabetic nephropathy, cerebral infarction and myocardial infarction. This patient was first diagnosed as having gastric cancer in 2007 but surgery and chemotherapy were contraindicated due to his poor physical status and poor renal function, respectively, owing to the anticipated side effects. The patient was referred to our institution after hearing of PDT in 2009. He was treated with 1 course of porfimer sodium PDT and 3 courses of talaporfin sodium PDT with photodynamic diagnosis (PDD) during the period from September, 2009 to June, 2011.
RESULTS
The massive gastric cancer located in the cardia was successfully treated with 4 PDT sessions without any serious complications; therefore the patient was able to orally ingest food until his death due to natural causes other than the cancer, in October, 2011.
CONCLUSION
Talaporfin sodium PDT is safe and effective treatment for advanced-aged patients suffering from inoperable gastric cancer.
PubMed: 25368446
DOI: 10.5978/islsm.14-OR-16 -
BMC Cancer Feb 2018Accumulating evidence suggest that autophagy plays a pivotal role in various anticancer therapies, including photodynamic therapy (PDT), acting as a pro-death or...
BACKGROUND
Accumulating evidence suggest that autophagy plays a pivotal role in various anticancer therapies, including photodynamic therapy (PDT), acting as a pro-death or pro-survival mechanism in a context-dependent manner. Therefore, we aimed to determine the role of autophagy in Photofrin-based PDT.
METHODS
In vitro cytotoxic/cytostatic effects of PDT were evaluated with crystal violet cell viability assay. Autophagy induction was analyzed by immunoblotting and immunofluorescence using anti-LC3 antibody. Autophagy was inhibited by shRNA-mediated ATG5 knockdown or CRISPR/Cas9-mediated ATG5 knockout. Apoptosis was assessed by flow cytometry analysis of propidium iodide and anexin V-positive cells as well as by detection of cleaved PARP and caspase 3 proteins using immunoblotting. Protein carbonylation was evaluated by the 2,4-dinitrophenylhydrazine (DNPH) method.
RESULTS
Photofrin-PDT leads to robust autophagy induction in two cancer cell lines, Hela and MCF-7. shRNA-mediated knockdown of ATG5 only partially blocks autophagic response and only marginally affects the sensitivity of Hela and MCF-7 cells to PDT. ATG5 knockout in HeLa cell line utilizing CRISPR/Cas9 genome editing results in increased PDT-mediated cytotoxicity, which is accompanied by an enhanced apoptotic response and increased accumulation of carbonylated proteins.
CONCLUSIONS
Altogether, these observations imply that autophagy contributes to Photofrin-PDT resistance by enabling clearance of carbonylated and other damaged proteins. Therefore, autophagy inhibition may serve as a strategy to improve PDT efficacy.
Topics: Antineoplastic Agents; Autophagy; Autophagy-Related Protein 5; Cell Line, Tumor; Cell Survival; Dihematoporphyrin Ether; Gene Expression; Gene Knockdown Techniques; Gene Targeting; Humans; Light; Photochemotherapy; Photosensitizing Agents; RNA Interference; RNA, Small Interfering
PubMed: 29463237
DOI: 10.1186/s12885-018-4126-y -
Physics in Medicine and Biology Dec 2017Photosensitizer fluorescence excited by photodynamic therapy (PDT) treatment light can be used to monitor the in vivo concentration of the photosensitizer and its...
Photosensitizer fluorescence excited by photodynamic therapy (PDT) treatment light can be used to monitor the in vivo concentration of the photosensitizer and its photobleaching. The temporal integral of the product of in vivo photosensitizer concentration and light fluence is called PDT dose, which is an important dosimetry quantity for PDT. However, the detected photosensitizer fluorescence may be distorted by variations in the absorption and scattering of both excitation and fluorescence light in tissue. Therefore, correction of the measured fluorescence for distortion due to variable optical properties is required for absolute quantification of photosensitizer concentration. In this study, we have developed a four-channel PDT dose dosimetry system to simultaneously acquire light dosimetry and photosensitizer fluorescence data. We measured PDT dose at four sites in the pleural cavity during pleural PDT. We have determined an empirical optical property correction function using Monte Carlo simulations of fluorescence for a range of physiologically relevant tissue optical properties. Parameters of the optical property correction function for Photofrin fluorescence were determined experimentally using tissue-simulating phantoms. In vivo measurements of photosensitizer fluorescence showed negligible photobleaching of Photofrin during the PDT treatment, but large intra- and inter-patient heterogeneities of in vivo Photofrin concentration are observed. PDT doses delivered to 22 sites in the pleural cavity of 8 patients were different by 2.9 times intra-patient and 8.3 times inter-patient.
Topics: Clinical Trials, Phase II as Topic; Dihematoporphyrin Ether; Fluorescence; Humans; Mesothelioma; Monte Carlo Method; Phantoms, Imaging; Photochemotherapy; Photosensitizing Agents; Pleural Neoplasms; Radiometry; Randomized Controlled Trials as Topic; Spectrometry, Fluorescence
PubMed: 29106380
DOI: 10.1088/1361-6560/aa9874