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Spatiotemporal metabolic dynamics of the photosensitizer talaporfin sodium in carcinoma and sarcoma.Cancer Science Feb 2021Photodynamic therapy (PDT) using the photosensitizer talaporfin sodium (talaporfin) is a new mode of treatment for cancer. However, the metabolic mechanism of talaporfin...
Photodynamic therapy (PDT) using the photosensitizer talaporfin sodium (talaporfin) is a new mode of treatment for cancer. However, the metabolic mechanism of talaporfin has not been clarified. Thus, we investigated the uptake, transportation, and elimination mechanisms of talaporfin in carcinoma and sarcoma. The results showed that talaporfin co-localized in early endosomes and lysosomes. Talaporfin uptake was via clathrin- and caveolae-dependent endocytosis and a high amount of intracellular ATP was essential. Inhibition of lysosomal enzymes maintained intracellular talaporfin levels. Inhibition of K-Ras signaling reduced talaporfin uptake in carcinoma and sarcoma cell lines. Talaporfin was taken up by clathrin- and caveolae-dependent endocytosis, translocated from early endosomes to lysosomes, and finally degraded by lysosomes. We also demonstrated that ATP is essential for the uptake of talaporfin and that activation of K-Ras is involved as a regulatory mechanism. These results provide new insights into the metabolism of talaporfin in cancer cells for the enhancement of PDT for carcinoma and sarcoma.
Topics: Carcinoma; Cell Line, Tumor; Humans; Photosensitizing Agents; Porphyrins; Sarcoma
PubMed: 33190360
DOI: 10.1111/cas.14735 -
Journal of Clinical Medicine Jun 2021Photodynamic therapy (PDT) using a conventional photosensitizer was approved for esophageal cancer in the early 1990s; however, it was replaced by other conventional... (Review)
Review
Photodynamic therapy (PDT) using a conventional photosensitizer was approved for esophageal cancer in the early 1990s; however, it was replaced by other conventional treatment modalities in clinical practice because of the high frequency of cutaneous phototoxicity and esophageal stricture after the procedure. The second-generation photosensitizer, talaporfin sodium, which features more rapid clearance from the body, was developed to reduce skin phototoxicity, and talaporfin sodium can be excited at longer-wavelength lights comparing with a conventional photosensitizer. Endoscopic PDT using talaporfin sodium was initially developed for the curative treatment of central-type early lung cancer in Japan, and was approved in the early 2000s. After preclinical experiments, PDT using talaporfin sodium was investigated for patients with local failure after chemoradiotherapy, which was the most serious unmet need in the practice of esophageal cancer. According to the favorable results of a multi-institutional clinical trial, PDT using talaporfin sodium was approved as an endoscopic salvage treatment for patients with local failure after chemoradiotherapy for esophageal cancer. While PDT using talaporfin sodium is gradually spreading in clinical practice, further evaluation at the point of clinical benefit is necessary to determine the importance of PDT in the treatment of esophageal cancer.
PubMed: 34202917
DOI: 10.3390/jcm10132785 -
Molecules (Basel, Switzerland) Apr 2023Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 () are presented. NPe6, also designated as Laserphyrin, Talaporfin,... (Review)
Review
Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 () are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, esophageal, and brain cancers. After the initial misidentification of the structure of this chlorin-e aspartic acid conjugate as (), NMR and other synthetic procedures described herein arrived at the correct structure (), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e chemistry (including the intramolecular formation of an anhydride ()) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 13 (formic), 15 (acetic), and 17 (propionic) of chlorin e (). Cellular investigations of several amino acid conjugates of chlorin-e revealed that the 13-aspartylchlorin-e derivative is more phototoxic than its 15- and 17-regioisomers, in part due to its nearly linear molecular conformation.
Topics: Humans; Photosensitizing Agents; Photochemotherapy; Porphyrins; Amino Acids; Aspartic Acid; Chlorophyllides
PubMed: 37110713
DOI: 10.3390/molecules28083479 -
Clinical Endoscopy Jul 2021Photodynamic therapy, a curative local treatment for esophageal squamous cell carcinoma, involves a photosensitizing drug (photosensitizer) with affinity for tumors and... (Review)
Review
Photodynamic therapy, a curative local treatment for esophageal squamous cell carcinoma, involves a photosensitizing drug (photosensitizer) with affinity for tumors and a photodynamic reaction triggered by laser light. Previously, photodynamic therapy was used to treat superficial esophageal squamous cell carcinoma judged to be difficult to undergo endoscopic resection. Recently, photodynamic therapy has mainly been performed for local failure after chemoradiotherapy. Although surgery is the most promising treatment for local failure after chemoradiotherapy, its morbidity and mortality rates are high. Endoscopic resection is feasible for local failure after chemoradiotherapy but requires advanced skills, and its indication is limited to within the submucosal layer by depth. Photodynamic therapy is less invasive than surgery and has a wider indication than endoscopic resection. Porfimer sodium (a first-generation photosensitizer) causes a high frequency of side effects related to photosensitivity and requires the long-term sun-shade period. Talaporfin (a second-generation photosensitizer) requires a much shorter sun-shade period than porfimer sodium. Photodynamic therapy will profoundly change treatment strategies for local failure after chemoradiotherapy.
PubMed: 32422695
DOI: 10.5946/ce.2020.073 -
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 -
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 -
Medicina (Kaunas, Lithuania) Nov 2023: This review paper highlights the key alternatives to the blue dye/radioisotope method of sentinel lymph node biopsy (SLNB). It analyses the research available on these... (Review)
Review
: This review paper highlights the key alternatives to the blue dye/radioisotope method of sentinel lymph node biopsy (SLNB). It analyses the research available on these alternative methods and their outcomes compared to the traditional techniques. : This review focused on fifteen articles, of which five used indocyanine green (ICG) as a tracer, four used magnetic tracers, one used one-step nucleic acid amplification (OSNA) and Metasin (quantitative reverse transcriptase-polymerase chain reaction), one used the photosensitiser talaporfin sodium, one used sulphur hexafluoride gas microbubbles, one used CT-guided lymphography and two focused on general SLNB technique reviews. : Of the 15 papers analysed, the sentinel node detection rates were 69-100% for indocyanine green, 91.67-100% for magnetic tracers, 81% for talaporfin sodium, 9.3-55.2% for sulphur hexafluoride gas microbubbles, 90.5% for CTLG and 82.7-100% for one-step nucleic acid amplification. : Indocyanine green fluorescence (ICG) and magnetic tracers have been proven non-inferior to traditional blue dye and isotope regarding SLNB localisation. Further studies are needed to investigate the use of these techniques in conjunction with each other and the possible use of language learning models. Dedicated studies are required to assess cost efficacy and longer-term outcomes.
Topics: Humans; Female; Sentinel Lymph Node Biopsy; Indocyanine Green; Lymphatic Metastasis; Sulfur Hexafluoride; Sentinel Lymph Node; Breast Neoplasms; Nucleic Acids; Lymph Nodes
PubMed: 38138180
DOI: 10.3390/medicina59122077 -
Pharmaceutics Feb 2022Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of...
Recurrent glioblastoma (GBM) remains one of the most challenging clinical issues, with no standard treatment and effective treatment options. To evaluate the efficacy of talaporfin sodium (TS) mediated photodynamic therapy (PDT) as a new treatment for this condition, we retrospectively analyzed 70 patients who underwent surgery with PDT (PDT group) for recurrent GBM and 38 patients who underwent surgery alone (control group). The median progression-free survival (PFS) in the PDT and control groups after second surgery was 5.7 and 2.2 months, respectively ( = 0.0043). The median overall survival (OS) after the second surgery was 16.0 and 12.8 months, respectively ( = 0.031). Both univariate and multivariate analyses indicated that surgery with PDT and a preoperative Karnofsky Performance Scale were significant independent prognostic factors for PFS and OS. In the PDT group, there was no significant difference regarding PFS and OS between patients whose previous pathology before recurrence was already GBM and those who had malignant transformation to GBM from lower grade glioma. There was also no significant difference in TS accumulation in the tumor between these two groups. According to these results, additional PDT treatment for recurrent GBM could have potential survival benefits and its efficacy is independent of the pre-recurrence pathology.
PubMed: 35214085
DOI: 10.3390/pharmaceutics14020353 -
Cancers Aug 2020Photodynamic therapy (PDT) is an attractive cancer treatment modality. Talaporfin sodium, a second-generation photosensitizer, results in lower systemic toxicity and...
Photodynamic therapy (PDT) is an attractive cancer treatment modality. Talaporfin sodium, a second-generation photosensitizer, results in lower systemic toxicity and relatively better selective tumor destruction than first-generation photosensitizers. However, the mechanism through which PDT induces vascular shutdown is unclear. In this study, the in vitro effects of talaporfin sodium-based PDT on human umbilical vein endothelial cells (HUVECs) were determined through cell viability and endothelial tube formation assays, and evaluation of the tubulin and F-actin dynamics and myosin light chain (MLC) phosphorylation. Additionally, the effects on tumor blood flow and tumor vessel destruction were assessed in vivo. In the HUVECs, talaporfin sodium-based PDT induced endothelial tube destruction and microtubule depolymerization, triggering the formation of F-actin stress fibers and a significant increase in MLC phosphorylation. However, pretreatment with the Rho-associated protein kinase (ROCK) inhibitor, Y27632, completely prevented PDT-induced stress fiber formation and MLC phosphorylation. The in vivo analysis and pathological examination revealed that the PDT had significantly decreased the tumor blood flow and the active area of the tumor vessel. We concluded that talaporfin sodium-based PDT induces the shutdown of existing tumor vessels via the RhoA/ROCK pathway by activating the Rho-GTP pathway and decreasing the tumor blood flow.
PubMed: 32825648
DOI: 10.3390/cancers12092369 -
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