Photodynamic therapy using talaporfin sodium (Laserphyrin) for bile duct carcinoma: A preliminary clinical trial
Division of Surgical Oncology and Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. . Anticancer research
(Impact Factor: 1.83).
The efficacy of adjuvant photodynamic therapy (PDT) using the new photosensitizer, talaporfin sodium (TPS), was assessed in 7 patients with bile duct carcinoma (BDC). The 664-nm semiconductor laser (100 J/cm(2)) was applied through endoscopy to the tumor lesion within 6 h after injection of TPS. Cases included three non-resectable and 4 resected BDC with remnant cancer cells at the bile duct stump. Radiated lesions exhibited mild inflammatory responses. Locally advanced tumor occluding bile duct was relieved by PDT and patency was maintained for 16 months. Two patients developed mild photodermatitis but no severe morbidity. One patient died of other disease, and two patients died of liver metastasis within 6 months, but local recurrence was not observed. Three patients maintained cancer-free survival for 6-13 months. One patient survived with good status for 24 months. Adjuvant TPS-PDT is a safe and useful treatment for local control of BDC. Compared to the conventional PDT, the patient's quality of life is remarkably improved.
Available from: Hirofumi Matsui
- "Talaporfin sodium is a new photosensitizer for photodynamic therapy (PDT) in the lung.(22) The clinical application of PDT will be expanded to other tissues in the near future.(22,23) For the treatment of malignant glioma, talaporfin sodium has progressed to a phase II clinical study, and the safety and therapeutic effects of talaporfin have been reported.(24–27) "
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ABSTRACT: The mechanism of tumor-specific porphyrin accumulation is not clear. We investigated the expression of proton-coupled folate transporter SLC46A1 in glioma and aimed to clarify the relationship between tumor fluorescence and SLC46A1 expression.We confirmed the expression of SLC46A1 in surgical specimens from 24 glioma patients by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). We also investigated SLC46A1 expression in glioma cell lines by RT-PCR. The cellular uptake of hematoporphyrin derivative in vitro was measured with a microplate reader and fluorescence microscope. In these experiments, we used three human malignant glioma cell lines: U87, U251 and T98G. Immunohistochemistry showed SLC46A1 positivity in the malignant tumor lesion of each specimen. Strong positive SLC46A1 expression was observed in 33% of grade IV, 22% of grade III and 17% of grade II gliomas. All four randomly obtained malignant glioma frozen sections expressed SLC46A1 mRNA by RT-PCR. In vitro, U87 showed the least SLC46A1 expression, U251 was intermediate, and T98G showed the most expression. The amount of hematoporphyrin derivative (HpD) cellular uptake correlated with SLC46A1 expression. These results suggest that the accumulation of HpD in glioma cells is related to SLC46A1 function and SLC46A1 is involved in the mechanism of glioma fluorescence.
Available from: Masahide Kuroki
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ABSTRACT: Photodynamic therapy (PDT) is a well-established clinical treatment modality for various diseases, including cancer. It involves the topical or systemic administration of a photosensitizer, followed by selective irradiation of the target lesion with a specific wavelength of non-ionizing light, which triggers oxidative photodamage and subsequent death of the targeted cells. Due to this two-step therapeutic process, PDT is a safe and minimally-invasive therapy. Nevertheless, classical non-targeted photosensitizers lack sufficient tumor selectivity and are taken up in the neighboring normal tissues, resulting in undesirable adverse effects. To overcome this obstacle, diverse tumor-targeting approaches have been developed. In this article, we discuss the current strategies and rationale regarding tumor-targeted PDT.
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ABSTRACT: This article reviews the more recent patents in three kinds of therapeutic strategies using the application of visible light to irradiate photosensible substances (PSs) of different natures. The light-activation of these PSs is directly responsible for the desired therapeutic effects. This group of light therapies includes photodynamic therapy (PDT), photothermal therapy (PTT) and photoimmunotherapy (PIT). Therapeutic mechanisms triggered by the activation of the PSs depend basically (though not exclusively) on the release of reactive oxygen species (ROS) and the activation of immune responses (PDT and PIT) or the local generation of heat (PTT). The main difference between PIT and PDT is that in PIT, monoclonal antibodies (MABs) are associated to PSs to improve the selective binding of the PSs to the target tissues. All these therapeutic strategies offer the possibility of destroying tumor tissue without damaging the surrounding healthy tissue, which is not achievable with chemotherapy or radiotherapy. PDT is also used as an alternative or adjuvant antimicrobial therapy together with the traditional antibiotic therapy since these organisms are unlikely to develop resistance to the ROS induced by PDT. Furthermore, PDT also induces an immune response against bacterial pathogens. The current challenge in PDT, PIT and PTT is to obtain the highest level of selectivity to act on targeted sick tissues with the minimum effects on the surrounding healthy tissue. The development of new PSs with high affinity for specific tissues, new PSs-MABs conjugates to bind to specific kinds of tumors, and new light-sensible nanoparticles with low toxicity, will increase the clinical utility of these therapies.
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