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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 -
Neurologia Medico-chirurgica 2016Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage... (Review)
Review
Photodynamic therapy (PDT) using talaporfin sodium together with a semiconductor laser was approved in Japan in October 2003 as a less invasive therapy for early-stage lung cancer. The author believes that the principle of PDT would be applicable for controlling the invading front of malignant brain tumors and verified its efficacy through experiments using glioma cell lines and glioma xenograft models. An investigator-initiated clinical study was jointly conducted with Tokyo Women's Medical University with the support of the Japan Medical Association. Patient enrollment was started in May 2009 and a total of 27 patients were enrolled by March 2012. Of 22 patients included in efficacy analysis, 13 patients with newly diagnosed glioblastoma showed progression-free survival of 12 months, progression-free survival at the site of laser irradiation of 20 months, 1-year survival of 100%, and overall survival of 24.8 months. In addition, the safety analysis of the 27 patients showed that adverse events directly related to PDT were mild. PDT was approved in Japan for health insurance coverage as a new intraoperative therapy with the indication for malignant brain tumors in September 2013. Currently, the post-marketing investigation in the accumulated patients has been conducted, and the preparation of guidelines, holding training courses, and dissemination of information on the safe implementation of PDT using web sites and videos, have been promoted. PDT is expected to be a breakthrough for the treatment of malignant glioma as a tumor cell-selective less invasive therapy for the infiltrated functional brain area.
Topics: Brain Neoplasms; Clinical Trials as Topic; Glioblastoma; Humans; Photochemotherapy
PubMed: 26888042
DOI: 10.2176/nmc.ra.2015-0296 -
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 -
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 -
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