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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 -
Recent Studies in Photodynamic Therapy for Cancer Treatment: From Basic Research to Clinical Trials.Pharmaceutics Aug 2023Photodynamic therapy (PDT) is an emerging and less invasive treatment modality for various types of cancer. This review provides an overview of recent trends in PDT... (Review)
Review
Photodynamic therapy (PDT) is an emerging and less invasive treatment modality for various types of cancer. This review provides an overview of recent trends in PDT research, ranging from basic research to ongoing clinical trials, focusing on different cancer types. Lung cancer, head and neck cancer, non-melanoma skin cancer, prostate cancer, and breast cancer are discussed in this context. In lung cancer, porfimer sodium, chlorin e6, and verteporfin have shown promising results in preclinical studies and clinical trials. For head and neck cancer, PDT has demonstrated effectiveness as an adjuvant treatment after surgery. PDT with temoporfin, redaporfin, photochlor, and IR700 shows potential in early stage larynx cancer and recurrent head and neck carcinoma. Non-melanoma skin cancer has been effectively treated with PDT using methyl aminolevulinate and 5-aminolevulinic acid. In prostate cancer and breast cancer, PDT research is focused on developing targeted photosensitizers to improve tumor-specific uptake and treatment response. In conclusion, PDT continues to evolve as a promising cancer treatment strategy, with ongoing research spanning from fundamental investigations to clinical trials, exploring various photosensitizers and treatment combinations. This review sheds light on the recent advancements in PDT for cancer therapy and highlights its potential for personalized and targeted treatments.
PubMed: 37765226
DOI: 10.3390/pharmaceutics15092257 -
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 -
Applied Biochemistry and Biotechnology Dec 2023Gastric cancer is the world's second leading cause of cancer-related fatalities, with the epidemiology changing over the previous several decades. FOXOs are the O...
Gastric cancer is the world's second leading cause of cancer-related fatalities, with the epidemiology changing over the previous several decades. FOXOs are the O subfamily of the forkhead box (FOX) transcription factor family, which consists of four members: FOXO1, FOXO3, FOXO4, and FOXO6. FOXO6 mRNA and protein levels are increased in gastric cancer tissues. FOXO6 forced overexpression enhances gastric cancer cell growth, while knockdown decreases proliferation. In our study, the GEPIA, Kaplan-Meier, KEGG, and STRING databases were used to determine FOXO6 mRNA expression, overall survival ratio, interactive pathways, and top 10 associated proteins in gastric cancer respectively. Due to the lack of a solved structure for FOXO6, homology modeling was performed to obtain a 3D structure model, and we used anti-cancer drugs and small molecules to target FOXO6 for identifying a potential selective FOXO6 inhibitor. The chemical composition of the proteins and ligands has a significant impact on docking procedure performance. With this in mind, a critical evaluation of the performance of three regularly used docking routines was carried out: MVD, AutoDock Vina in PyRx, and ArgusLab. The binding affinities, docking scores, and intermolecular interactions were used as assessment criteria. In the study, the porfimer sodium showed excellent binding affinity to the FOXO6 protein. The major three docking software packages were used to analyze the scoring/H-bonding energy and intermolecular interactions. Based on the results, we concluded that FOXO6 was upregulated in gastric cancer and the ligand porfimer sodium emerges as a promising potential FOXO6 inhibitor to curtail gastric cancer progression.
Topics: Humans; Stomach Neoplasms; Dihematoporphyrin Ether; Drug Repositioning; Early Detection of Cancer; Forkhead Transcription Factors; RNA, Messenger
PubMed: 37086375
DOI: 10.1007/s12010-023-04490-1 -
Photodiagnosis and Photodynamic Therapy Mar 2023Oral squamous cell carcinoma (OSCC) treatment consists mainly of surgery, chemotherapy, and radiotherapy, alone or in combination. Epithelial dysplasia (ED) is also...
BACKGROUND
Oral squamous cell carcinoma (OSCC) treatment consists mainly of surgery, chemotherapy, and radiotherapy, alone or in combination. Epithelial dysplasia (ED) is also treated with surgery. However, these treatments can induce functional and/or aesthetic disturbances. Photodynamic therapy (PDT) can preserve organs. Although short-term studies have shown good progress, long-term evaluations have not yet been conducted. This study aimed to clarify the long-term effects of PDT on OSCC and ED.
METHODS
Patients who underwent PDT with the first (porfimer sodium) or second generation photosensitizers (talaporfin sodium) for early OSCC (T1 and T2) and ED were included in this study. The long-term prognosis was assessed.
RESULTS
Twenty-three patients were included. Complete response (CR) was observed in 19 patients (82.6%) and partial response (PR) in 4 patients (17.4%) 4 weeks after PDT. Regarding long-term progress, local region recurrence occurred in 11 of 19 CR cases (57.9%), and the term of recurrence was 27.4 ± 30.4 months. Surgical resection was performed in all local recurrence and PR cases, and 3 patients died of the underlying disease.
CONCLUSIONS
PDT provides a good outcome in the short term, but its long-term effects are limited.
Topics: Humans; Photosensitizing Agents; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Photochemotherapy; Mouth Neoplasms; Carcinoma in Situ; Head and Neck Neoplasms; Treatment Outcome; Neoplasm Recurrence, Local
PubMed: 36535598
DOI: 10.1016/j.pdpdt.2022.103246 -
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 -
Frontiers in Oncology 2022The poor prognosis of patients with esophageal cancer leads to the constant search for new ways of treatment of this disease. One of the methods used in high-grade... (Review)
Review
The poor prognosis of patients with esophageal cancer leads to the constant search for new ways of treatment of this disease. One of the methods used in high-grade dysplasia, superficial invasive carcinoma, and sometimes palliative care is photodynamic therapy (PDT). This method has come a long way from the first experimental studies to registration in the treatment of esophageal cancer and is constantly being improved and refined. This review describes esophageal cancer, current treatment methods, the introduction to PDT, the photosensitizers (PSs) used in esophageal carcinoma PDT, PDT in squamous cell carcinoma (SCC) of the esophagus, and PDT in invasive adenocarcinoma of the esophagus. For this review, research and review articles from PubMed and Web of Science databases were used. The keywords used were "photodynamic therapy in esophageal cancer" in the years 2000-2020. The total number of papers returned was 1,000. After the review was divided into topic blocks and the searched publications were analyzed, 117 articles were selected.
PubMed: 36465381
DOI: 10.3389/fonc.2022.1024576 -
Photochemistry and Photobiology Mar 2023Photodynamic therapy (PDT) has been used to treat malignant pleural mesothelioma. Current practice involves delivering light to a prescribed light fluence with a point...
Photodynamic therapy (PDT) has been used to treat malignant pleural mesothelioma. Current practice involves delivering light to a prescribed light fluence with a point source, monitored by eight isotropic detectors inside the pleural cavity. An infrared (IR) navigation system was used to track the location of the point source throughout the treatment. The recorded data were used to reconstruct the pleural cavity and calculate the light fluence to the whole cavity. An automatic algorithm was developed recently to calculate the detector positions based on recorded data within an hour. This algorithm was applied to patient case studies and the calculated results were compared to the measured positions, with an average difference of 2.5 cm. Calculated light fluence at calculated positions were compared to measured values. The differences between the calculated and measured light fluence were within 14% for all cases, with a fixed scattering constant and a dual correction method. Fluence-surface histogram (FSH) was calculated for photofrin-mediated PDT to be able to cover 80% of pleural surface area to 50 J cm (83.3% of 60 J cm ). The study demonstrates that it will be possible to eliminate the manual measurement of the detector positions, reducing the patient's time under anesthesia.
Topics: Humans; Photochemotherapy; Mesothelioma; Mesothelioma, Malignant; Dihematoporphyrin Ether; Algorithms
PubMed: 35996976
DOI: 10.1111/php.13697 -
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