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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 -
Cancer Science Sep 2004The sonodynamically induced antitumor effect of porfimer sodium (PF) was evaluated on a chemically induced mammary tumor in Sprague-Dawley rats. The timing of 24 h after...
The sonodynamically induced antitumor effect of porfimer sodium (PF) was evaluated on a chemically induced mammary tumor in Sprague-Dawley rats. The timing of 24 h after the administration of PF was chosen for the ultrasonic exposure, based on pharmacokinetic analysis of the PF concentrations in the tumor, plasma, skin and muscle. At a PF dose not less than 2.5 mg/kg and at a free-field ultrasonic intensity not less than 3 W/cm2, the synergistic effect between PF administration and ultrasonic exposure on the tumor growth inhibition was significant. The ultrasonic intensity showed a relatively sharp threshold for the synergistic antitumor effect, which is typical of an ultrasonic effect mediated by acoustic cavitation. These results suggest that PF is a potentially useful as a sonosensitizer for sonodynamic treatment of chemically induced tumors.
Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Antineoplastic Agents; Carcinogens; Combined Modality Therapy; Dihematoporphyrin Ether; Female; Mammary Neoplasms, Animal; Rats; Rats, Sprague-Dawley; Tissue Distribution; Ultrasonic Therapy
PubMed: 15471564
DOI: 10.1111/j.1349-7006.2004.tb03259.x -
Annals of Translational Medicine Mar 2014Photodynamic therapy (PDT) is a promising treatment option for local control of remnant cancer after surgical resection or biliary stenosis by the unresectable tumor in...
BACKGROUND
Photodynamic therapy (PDT) is a promising treatment option for local control of remnant cancer after surgical resection or biliary stenosis by the unresectable tumor in patients with bile duct carcinomas (BDC). To achieve effective tumor necrosis, an appropriate approach to laser irradiation is necessary.
METHODS
The efficacy of endoscopy-guided PDT using porfimer (n=12) or talaporfin sodium (n=13) was investigated by evaluating the transhepatic biliary routes and endoscopic retrograde biliary (ERB) routes in 25 patients with BDC.
RESULTS
Diseases included perihilar intrahepatic cholangiocarcinoma (ICC) in four patients, extrahepatic BDCs in 19 and ampular carcinoma (AC) in two patients. Adjuvant PDT after surgical resection was performed in 18 patients, and PDT for tumor biliary stenosis was performed in seven. In patients undergoing surgical resections, the mean period between the operation and PDT was 87±42 days. In patients who underwent prior surgical resections, the transhepatic route was used in five (28%), the jejunal loop was used in 11 (61%), the T-tube route was used in one, and the endoscopic retrograde cholangiography (ERC) route via papilla Vater was used in one. In unresectable BDC, the ERC route was used in four patients (57%), and the transhepatic biliary route was used in three (43%). Endoscopic-guided PDT could not be performed in one patient because of a technical failure. Except for the complication of photosensitivity, endoscopy-related complications were not observed in any patients. Patients undergoing PDT with porfimer sodium had a significantly longer admission period compared to patients undergoing PDT with talaporfin sodium (36 vs. 5 days, respectively) (P<0.01).
CONCLUSIONS
PDT was safely and definitively performed using the endoscopy-guided approach via the transhepatic or ERC route. By considering the disadvantages of both routes, PDT must be adequately achieved for local control of BDC.
PubMed: 25332999
DOI: 10.3978/j.issn.2305-5839.2014.03.04 -
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 -
Technology in Cancer Research &... Aug 2003Invasive intracranial tumors, particularly malignant gliomas, are very difficult to eradicate surgically and carry a dismal prognosis. The vast majority relapse locally... (Review)
Review
Invasive intracranial tumors, particularly malignant gliomas, are very difficult to eradicate surgically and carry a dismal prognosis. The vast majority relapse locally indicating that their cure is dependent on radical and complete local excision. However, their ability to invade and hide among normal brain tissue, our inability to visualize and detect them, the low tolerance of brain tissue to ionizing radiation and the presence of the blood brain barrier are the main causes of our failure to eradicate them. Photodynamic detection with 100% specificity and more than 80% sensitivity offers an excellent chance of visualizing camouflaged tumor nests. Also, photodynamic therapy offers a very good chance of targeted destruction of the remaining tumor cells safely following surgical excision and may double the survival of patients harboring these awful tumors. More work needs to be done to refine this promising technology to exploit it to its full potential.
Topics: Aminolevulinic Acid; Brain Neoplasms; Clinical Trials as Topic; Dihematoporphyrin Ether; Glioma; Humans; Lasers; Mesoporphyrins; Necrosis; Photochemotherapy; Photosensitizing Agents; Prognosis
PubMed: 12892512
DOI: 10.1177/153303460300200404 -
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 -
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 -
Journal of Biomedical Optics Jan 2024Photodynamic therapy (PDT) is an established cancer treatment utilizing light-activated photosensitizers (PS). Effective treatment hinges on the PDT dose-dependent on PS...
SIGNIFICANCE
Photodynamic therapy (PDT) is an established cancer treatment utilizing light-activated photosensitizers (PS). Effective treatment hinges on the PDT dose-dependent on PS concentration and light fluence-delivered over time. We introduce an innovative eight-channel PDT dose dosimetry system capable of concurrently measuring light fluence and PS concentration during treatment.
AIM
We aim to develop and evaluate an eight-channel PDT dose dosimetry system for simultaneous measurement of light fluence and PS concentration. By addressing uncertainties due to tissue variations, the system enhances accurate PDT dosimetry for improved treatment outcomes.
APPROACH
The study positions eight isotropic detectors strategically within the pleural cavity before PDT. These detectors are linked to bifurcated fibers, distributing signals to both a photodiode and a spectrometer. Calibration techniques are applied to counter tissue-related variations and improve measurement accuracy. The fluorescence signal is normalized using the measured light fluence, compensating for variations in tissue properties. Measurements were taken in 78 sites in the pleural cavities of 20 patients.
RESULTS
Observations reveal minimal Photofrin concentration variation during PDT at each site, juxtaposed with significant intra- and inter-patient heterogeneities. Across 78 treated sites in 20 patients, the average Photofrin concentration for all 78 sites is , with a median concentration of . The average PDT dose for all 78 sites is , with a median dose of . A significant variation in PDT doses is observed, with a maximum difference of 3.1 times among all sites within one patient and a maximum difference of 9.8 times across all patients.
CONCLUSIONS
The introduced eight-channel PDT dose dosimetry system serves as a valuable real-time monitoring tool for light fluence and PS concentration during PDT. Its ability to mitigate uncertainties arising from tissue properties enhances dosimetry accuracy, thus optimizing treatment outcomes and bolstering the effectiveness of PDT in cancer therapy.
Topics: Humans; Dihematoporphyrin Ether; Photochemotherapy; Photosensitizing Agents; Radiometry
PubMed: 38223299
DOI: 10.1117/1.JBO.29.1.018001 -
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