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Annals of Translational Medicine Apr 2017Photodynamic therapy (PDT) is a non-invasive antitumor treatment that uses the combination of a photosensitizer, tissue oxygen, and visible light irradiation to produce... (Review)
Review
Photodynamic therapy (PDT) is a non-invasive antitumor treatment that uses the combination of a photosensitizer, tissue oxygen, and visible light irradiation to produce cytotoxic reactive oxygen species, predominantly singlet oxygen. Currently, first-generation PDT using porfimer sodium with an excimer dye laser, and second-generation PDT using talaporfin sodium PDT with a semiconductor laser are approved by health insurance for use in Japan. However, the cancer cell specificity and selectivity of these treatments are inadequate. Cancer cells consume higher levels of glucose than normal cells and this phenomenon is known as the Warburg effect. Thus, we developed a third-generation PDT, based on the Warburg effect, by synthesizing a novel photosensitizer, sugar-conjugated chlorin, with increased cancer cell-selective accumulation. Glucose-conjugated chlorin (G-chlorin) PDT showed significantly stronger antitumor effects than second-generation talaporfin PDT. We also found that PDT with G-chlorin induced immunogenic cell death which is characterized by the secretion, release, or surface exposure of damage-associated molecular patterns (DAMPs), including calreticulin (CRT) and the high-mobility group box 1 (HMGB1) protein. Mannose-conjugated chlorin (M-chlorin) PDT which targets the mannose receptors on the surface of cancer cells and tumor-associated macrophages (TAMs) in cancer tissue stroma also showed very strong antitumor effects. These novel PDTs using glucose or M-chlorins stand as new candidates for very effective, next-generation PDTs.
PubMed: 28616398
DOI: 10.21037/atm.2017.03.59 -
Bioengineering (Basel, Switzerland) Dec 2018To evaluate the effectiveness of photodynamic therapy occurring in the interstitial space of the myocardium, we estimated the interstitial concentration of talaporfin...
A Three-Compartment Pharmacokinetic Model to Predict the Interstitial Concentration of Talaporfin Sodium in the Myocardium for Photodynamic Therapy: A Method Combining Measured Fluorescence and Analysis of the Compartmental Origin of the Fluorescence.
To evaluate the effectiveness of photodynamic therapy occurring in the interstitial space of the myocardium, we estimated the interstitial concentration of talaporfin sodium in the canine myocardium by constructing a three-compartment pharmacokinetic model based on measured changes in talaporfin sodium plasma concentration and myocardial fluorescence. Differential rate equations of talaporfin sodium concentration in the plasma, interstitial space, and cell compartment were developed with individual compartment volume, concentration, and rate constants. Using measured volume ratios based on histological examinations, we defined that the myocardial fluorescence consisted of the linear addition of fluorescence generated from these three compartments. The rate constants were obtained by fitting to minimize the sum of the squared errors between the measured talaporfin sodium concentrations and the calculated concentrations divided by the number of data points using the conjugate gradient method in MATLAB. We confirmed that this fitting operation may be appropriate, because a coefficient of determination between the measured talaporfin sodium changes and the calculated concentrations using our equations was 0.99. Consequently, to estimate the interstitial concentration in the canine myocardium, we propose a three-compartment pharmacokinetic model construction methodology using measured changes in talaporfin sodium plasma concentration and changes in myocardial fluorescence.
PubMed: 30583456
DOI: 10.3390/bioengineering6010001 -
Yonago Acta Medica Feb 2021Talaporfin sodium photodynamic therapy (TS-PDT) for local failure after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma has recently been...
BACKGROUND
Talaporfin sodium photodynamic therapy (TS-PDT) for local failure after chemoradiotherapy (CRT) in patients with esophageal squamous cell carcinoma has recently been reported to be highly effective and less invasive, compared to other treatment modalities. TS-PDT was recently introduced at the Tottori University Hospital, Japan. The aim of this study is to clarify the efficacy and safety of PDT in our hospital.
METHODS
This was a single-center observational study. We examined eight cases of TS-PDT performed between January 2016 and December 2019. The main endpoints were local complete remission (L-CR) rate and the adverse events. In addition, age, gender, histology, tumor location, TNM stage, tumor depth, irradiation dose, and overall survival (OS) were examined.
RESULTS
The patients included 7 men and a woman, with an average age of 72.1 years (range 63-82 years). The baseline clinical stages before CRT or radiotherapy were stage I in 1, stage II in 3, stage III in 3, and stage IVA in 1 patient. The T stage on endoscopic assessment before TS-PDT was T1 in 6 patients and T2 in 2 patients. Treatment outcomes and adverse events were evaluated. There were no treatment-related deaths, and no significant adverse events occurred intraoperatively or postoperatively. The L-CR rate was 7/8 (87.5%); T1 cases had 100% (6/6) L-CR, while T2 cases had 50% (1/2). The 2-year OS rates were 87%.
CONCLUSION
TS-PDT was observed to be safe and effective in the first eight cases of its application following its introduction in our hospital.
PubMed: 33642911
DOI: 10.33160/yam.2021.02.018 -
Journal of Clinical Medicine Jan 2023Photodiagnosis (PD) and photodynamic therapy (PDT) using the second-generation photosensitizer talaporfin sodium together with an exciting laser for primary intracranial...
First Clinical Report of the Intraoperative Macro- and Micro-Photodiagnosis and Photodynamic Therapy Using Talaporfin Sodium for a Patient with Disseminated Lumbar Medulloblastoma.
Photodiagnosis (PD) and photodynamic therapy (PDT) using the second-generation photosensitizer talaporfin sodium together with an exciting laser for primary intracranial malignant tumors is well recognized in Japan, and many medical institutions are introducing this new therapeutic option. In particular, intraoperative PDT using talaporfin sodium for infiltrating tumor cells in the cavity walls after the resection of malignant glioma is now covered by health insurance after receiving governmental approvement, and this method has been recommended in therapeutic guidelines for primary malignant brain tumors in Japan. On the other hand, experimental and clinical studies on the development of novel therapeutic strategies for malignant spinal cord tumors have not been reported to date, although their histological features are almost identical to those of intracranial malignant tumors. Therefore, the clinical outcomes of malignant spinal cord tumors have been less favorable than those of malignant brain tumors. In this report, we performed the PD and PDT using talaporfin sodium on a patient with a metastatic lumbar lesion that was detected on magnetic resonance image (MRI) 50 months after the resection of cerebellar medulloblastoma who presented with lumbago and sciatica. We were able to detect the target lesion in the conus medullaris using a surgical microscope, and detected the disseminated medulloblastoma cells floating in the cerebrospinal fluid using a compact fluorescence microscope. Furthermore, we performed PDT to the resected lumbar lesion with the adjuvant platinum-based chemotherapy, and the patient survived a meaningful life for more than 2 years after the lumbar surgery. This report describes the first case of a human patient in whom the efficacy of PD and PDT was demonstrated for a malignant spinal cord tumor.
PubMed: 36675360
DOI: 10.3390/jcm12020432 -
Brain Sciences Sep 2023On average, there are about 300,000 new cases of brain cancer each year. Studies have shown that brain and central nervous system tumors are among the top ten causes of... (Review)
Review
On average, there are about 300,000 new cases of brain cancer each year. Studies have shown that brain and central nervous system tumors are among the top ten causes of death. Due to the extent of this problem and the percentage of patients suffering from brain tumors, innovative therapeutic treatment methods are constantly being sought. One such innovative therapeutic method is photodynamic therapy (PDT). Photodynamic therapy is an alternative and unique technique widely used in dermatology and other fields of medicine for the treatment of oncological and nononcological lesions. Photodynamic therapy consists of the destruction of cancer cells and inducing inflammatory changes by using laser light of a specific wavelength in combination with the application of a photosensitizer. The most commonly used photosensitizers include 5-aminolevulinic acid for the enzymatic generation of protoporphyrin IX, Temoporfin-THPC, Photofrin, Hypericin and Talaporfin. This paper reviews the photosensitizers commonly used in photodynamic therapy for brain tumors. An overview of all three generations of photosensitizers is presented. Along with an indication of the limitations of the treatment of brain tumors, intraoperative photodynamic therapy and its possibilities are described as an alternative therapeutic method.
PubMed: 37759900
DOI: 10.3390/brainsci13091299 -
Molecular Therapy Oncolytics Mar 2023Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light irradiation. PDT induces...
Photodynamic therapy (PDT) is a relatively non-invasive anti-cancer therapy that employs a photosensitizer with a specific wavelength of light irradiation. PDT induces direct cell killing and enhancement effects on tumor immunity, but its underlying mechanism remains unknown. Here, we perform a basic analysis of the anti-tumor effect of talaporfin sodium (TS)-PDT as well as its synergism with the immune checkpoint inhibitor anti-programmed death 1 (anti-PD-1) antibody. We estimate the cell death mechanism induced by TS-PDT and the induction of damage-associated molecular patterns (DAMPs) by TS-PDT . We establish a syngeneic mouse model of bilateral flank tumors and verify the enhancement of the abscopal effect on the non-irradiated side. TS-PDT induced apoptosis, necrosis, and autophagy-associated cell death . TS-PDT induced the release and/or expression of DAMPs . Tumor growth was inhibited in the TS-PDT and anti-PD-1 antibody combination group compared with other single-treatment or non-treatment groups . In summary, TS-PDT induces the release and/or expression of DAMPs, indicating that it activates innate immunity. PD-1 blockage enhances the anti-tumor immunity induced by TS-PDT. Thus, our results demonstrate that the combination of TS-PDT and anti-PD-1 antibody can potentially be used for anti-tumor therapy.
PubMed: 36726602
DOI: 10.1016/j.omto.2022.12.009 -
Oncotarget Mar 2017Photodynamic therapy (PDT) showed promising efficacy for local failure after chemoradiotherapy (CRT) for esophageal cancer. However, PDT required long sun shade period....
A multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer.
Photodynamic therapy (PDT) showed promising efficacy for local failure after chemoradiotherapy (CRT) for esophageal cancer. However, PDT required long sun shade period. This study aimed to evaluate the safety and efficacy of PDT using second generation photosensitizer, talaporfin sodium for local failure after CRT. This was the multi-institutional non-randomized phase II study. Patients with histologically proven local failure limited within the muscularis propria after 50Gy or more radiotherapy (RT) for esophageal cancer were eligible. We set the primary endpoint as local complete response (L-CR) per patients. And, secondary endpoints were confirmed L-CR, local progression free survival (L-PFS), progression free survival (PFS), overall survival (OS), L-CR per lesions (Lesion L-CR), and confirmed Lesion L-CR. The PDT procedure commenced with intravenous administration of a 40 mg/m2 dose of talaporfin sodium followed by diode laser irradiation at a 664 nm wavelength. 26 eligible patients were enrolled and all were treated with PDT. Twenty three patients with 25 lesions were assessed L-CR after PDT; the L-CR rate per patients was 88.5% (95% CI: 69.8%-97.6%). No skin phototoxicity was observed, and no grade 3 or worse non-hematological toxicities related to PDT were observed. PDT using talaporfin sodium and a diode laser is a safe and curative salvage treatment for local failure after CRT or RT for patients with esophageal cancer.
Topics: Aged; Aged, 80 and over; Chemoradiotherapy; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Lasers, Semiconductor; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Photochemotherapy; Photosensitizing Agents; Porphyrins; Prognosis; Radiotherapy; Salvage Therapy; Survival Rate
PubMed: 28212527
DOI: 10.18632/oncotarget.14029 -
Journal of Clinical Medicine Feb 2021In 2015, the Japanese health insurance approved the use of a second-generation photodynamic therapy (PDT) using talaporfin sodium (TS); however, its cancer cell... (Review)
Review
In 2015, the Japanese health insurance approved the use of a second-generation photodynamic therapy (PDT) using talaporfin sodium (TS); however, its cancer cell selectivity and antitumor effects of TS PDT are not comprehensive. The Warburg effect describes the elevated rate of glycolysis in cancer cells, despite the presence of sufficient oxygen. Because cancer cells absorb considerable amounts of glucose, they are visible using positron emission tomography (PET). We developed a third-generation PDT based on the Warburg effect by synthesizing novel photosensitizers (PSs) in the form of sugar-conjugated chlorins. Glucose-conjugated (tetrafluorophenyl) chlorin (G-chlorin) PDT revealed significantly stronger antitumor effects than TS PDT and induced immunogenic cell death (ICD). ICD induced by PDT enhances cancer immunity, and a combination therapy of PDT and immune checkpoint blockers is expected to synergize antitumor effects. Mannose-conjugated (tetrafluorophenyl) chlorin (M-chlorin) PDT, which targets cancer cells and tumor-associated macrophages (TAMs), also shows strong antitumor effects. Finally, we synthesized a glucose-conjugated chlorin e6 (SC-N003HP) that showed 10,000-50,000 times stronger antitumor effects than TS (IC) in vitro, and it was rapidly metabolized and excreted. In this review, we discuss the potential and the future of next-generation cancer cell-selective PDT and describe three types of sugar-conjugated PSs expected to be clinically developed in the future.
PubMed: 33670714
DOI: 10.3390/jcm10040841 -
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 -
Biomaterials Research 2018Photodynamic therapy (PDT) is photo-treatment of malignant or benign diseases using photosensitizing agents, light, and oxygen which generates cytotoxic reactive oxygens... (Review)
Review
BACKGROUND
Photodynamic therapy (PDT) is photo-treatment of malignant or benign diseases using photosensitizing agents, light, and oxygen which generates cytotoxic reactive oxygens and induces tumour regressions. Several photodynamic treatments have been extensively studied and the photosensitizers (PS) are key to their biological efficacy, while laser and oxygen allow to appropriate and flexible delivery for treatment of diseases.
INTRODUCTION
In presence of oxygen and the specific light triggering, PS is activated from its ground state into an excited singlet state, generates reactive oxygen species (ROS) and induces apoptosis of cancer tissues. Those PS can be divided by its specific efficiency of ROS generation, absorption wavelength and chemical structure.
MAIN BODY
Up to dates, several PS were approved for clinical applications or under clinical trials. Photofrin® is the first clinically approved photosensitizer for the treatment of cancer. The second generation of PS, Porfimer sodium (Photofrin®), Temoporfin (Foscan®), Motexafin lutetium, Palladium bacteriopheophorbide, Purlytin®, Verteporfin (Visudyne®), Talaporfin (Laserphyrin®) are clinically approved or under-clinical trials. Now, third generation of PS, which can dramatically improve cancer-targeting efficiency by chemical modification, nano-delivery system or antibody conjugation, are extensively studied for clinical development.
CONCLUSION
Here, we discuss up-to-date information on FDA-approved photodynamic agents, the clinical benefits of these agents. However, PDT is still dearth for the treatment of diseases in specifically deep tissue cancer. Next generation PS will be addressed in the future for PDT. We also provide clinical unmet need for the design of new photosensitizers.
PubMed: 30275968
DOI: 10.1186/s40824-018-0140-z