Molecular determinants of photodynamic therapy for lung cancers

Usuda, Jitsuo; Ichinose, Shuji; Ishizumi, Taichirou; Ohtani, Kazuhiro; Inoue, Tatsuya; Maehara, Sachio; Imai, Kentarou; Shima, K; Ohira, Tetsuya; Kato, Harubumi; Ikeda, Norihiko

doi:10.1002/lsm.21097

Cited by 12 publications

(11 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, as in performing PDT with TS, large vessels must be kept shielded from the treatment laser to avoid embolism. In fact, microvasculature damage and its subsequent effect on the vascular system surrounding the tumor was identified as a basis for TS’s antitumor activity when it was first introduced in Japan for treating early stage lung cancer ( 27 ). The fluorescence emission from blood vessels might explain why the area under the ROC curve (0.792) for TS in our study was a bit smaller than that reported for 5-ALA (0.88) ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Intraoperative Photodynamic Diagnosis Using Talaporfin Sodium Simultaneously Applied for Photodynamic Therapy against Malignant Glioma: A Prospective Clinical Study

et al. 2018

View full text Add to dashboard Cite

ObjectiveThe goal of this study was to demonstrate the feasibility of intraoperative photodynamic diagnosis (PDD) of malignant glioma using the fluorescence from talaporfin sodium (TS), which is used simultaneously for photodynamic therapy (PDT).MethodsPatients with suspected primary malignant glioma who were eligible for surgical removal of the tumor and PDT with TS were enrolled in this prospective study. Tissue samples were obtained from the contrast-enhanced (CE) region and from the surrounding non-contrast-enhanced (NCE) marginal tissue at the boundary between the tumor and normal tissue. The excised samples were set into a fluorescence measurement system, which consisted of a semiconductor laser with a 400-nm wavelength for excitation, and a compact spectrometer for detection, which were applied and received through a custom-made probe consisting of coaxial optical fibers. The fluorescence spectrum was obtained, and peak intensity was calculated. Tumor cellularity was histopathologically analyzed and semi-quantitatively classified into four (0–3) categories.Results86 samples from 17 surgical cases were available for fluorescence measurement and analysis. The fluorescence from TS had a single peak at 664 nm that was easily distinguished from the 400-nm excitation light. Samples from the CE regions showed higher fluorescence intensity than those from the NCE regions (P < 0.001). DAPI staining and fluorescence microscopy confirmed that cells in the CE regions showed red fluorescence in their cytoplasm. The fluorescence was notably strong along vascular endothelium. CE samples from newly diagnosed versus recurrent cases showed no difference in fluorescence intensity (P = 0.26). Among all samples (CE and NCE combined), the fluorescence intensity was very high in those of histopathological class 3, and a trend of increased fluorescence according to histopathological class (P < 0.001) was shown. Differences between class 0 and 3 (P < 0.001), class 1 and 3 (P < 0.001), and class 2 and 3 (P = 0.018) were significant.ConclusionIntraoperative simultaneous PDD and PDT with TS can be performed for patients with malignant glioma. The blue excitation light that is used for 5-aminolevulinic acid PDD can be used for our technique (TS-PDD). The strong fluorescence from pathologically malignant tissues may be due at least in part to the involvement of microvascular structures.

show abstract

Section: Discussionmentioning

confidence: 99%

Intraoperative Photodynamic Diagnosis Using Talaporfin Sodium Simultaneously Applied for Photodynamic Therapy against Malignant Glioma: A Prospective Clinical Study

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Phenomena reported here will be examined under more pertinent pH and pO 2 conditions. Successful clinical protocols have utilized both NPe6 and BPD 21,22 . The sequential approach proposed here would therefore not involve any new photosensitizing agents of unknown efficacy.…”

Section: Implications and Conclusionmentioning

confidence: 99%

Increased efficacy of photodynamic therapy via sequential targeting

2014

View full text Add to dashboard Cite

Photokilling depends on the generation of death signals after photosensitized cells are irradiated. A variety of intracellular organelles can be targeted for photodamage, often with a high degree of specificity. We have discovered that a low level of photodamage directed against lysosomes can sensitize both a murine hepatoma cell line (in 2D culture) and an inflammatory breast cancer line of human origin (in a 3D model) to subsequent photodamage directed at mitochondria. Additional studies were carried out with hepatoma cells to explore possible mechanisms. The phototoxic effect of the 'sequential targeting' approach was associated with an increased apoptotic response. The low level of lysosomal photodamage did not lead to any detectable migration of Fe ++ from lysosomes to mitochondria or increased reactive oxygen species (ROS) formation after subsequent mitochondrial photodamage. Instead, there appears to be a signal generated that can amplify the pro-apoptotic effect of subsequent mitochondrial photodamage.

show abstract

“…Several preclinical studies and some clinical trials suggest that the use of PDT in combination with established treatments or with newly-developed modalities may be of benefit as compared to the individual modalities [20]. As PDT induces apoptosis, inflammatory reactions, immune reactions, and subsequently damage to the microvasculature around the tumor, interestingly, there is evidence now that the mechanisms responsible for the anticancer effects of various PS upon PDT somewhat differs, as in the example of Photofrin-PDT and NPe6-PDT [21]. Usuda J et al [21] examined the role of immunological reactions in the anti-tumor effects of PDT using cytokine-over-expressing cells and investigated whether the anti-apoptotic protein Bcl-2 may be a molecular target.…”

Section: Introductionmentioning

confidence: 99%

“…As PDT induces apoptosis, inflammatory reactions, immune reactions, and subsequently damage to the microvasculature around the tumor, interestingly, there is evidence now that the mechanisms responsible for the anticancer effects of various PS upon PDT somewhat differs, as in the example of Photofrin-PDT and NPe6-PDT [21]. Usuda J et al [21] examined the role of immunological reactions in the anti-tumor effects of PDT using cytokine-over-expressing cells and investigated whether the anti-apoptotic protein Bcl-2 may be a molecular target. They also investigated the association between ATP-binding cassette transporter protein-breast cancer-resistant protein (BCRP).…”

Section: Introductionmentioning

confidence: 99%

“…However, NPe6-PDT exerted a strong antitumor effect regardless of BCRP expression, and the complete response rate after NPe6-PDT was much higher than that after Photofrin-PDT. They concluded that NPe6-PDT may be superior to Photofrin-PDT for the treatment of lung caner, and individualized approaches to PDT based on the expression status of Bcl-2 and/or BCRP may improve the efficacy of PDT in patients with lung cancers [21].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Photodynamic therapy stimulates anti-tumor immune response in mouse models: the role of regulatory Tcells, anti-tumor antibodies, and immune attacks on brain metastases

et al. 2013

View full text Add to dashboard Cite

We have previously shown that photodynamic therapy mediated by a vascular regimen of benzoporphyrin derivative and 690nm light is capable of inducing a robust immune response in the mouse CT26.CL25 tumor model that contains a tumor-rejection antigen, beta-galactosidase (β-gal). For the first time we show that PDT can stimulate the production of serum IgG antibodies against the β-gal antigen. It is known that a common cause of death from cancer, particularly lung cancer, is brain metastases; especially the inoperable ones that do not respond to traditional cytotoxic therapies either. We asked whether PDT of a primary tumor could stimulate immune response that could attack the distant brain metastases. We have developed a mouse model of generating brain metastases by injecting CT26.CL25 tumor cells into the brain as well as injecting the same cancer cells under the skin at the same time. When the subcutaneous tumor was treated with PDT, we observed a survival advantage compared to mice that had untreated brain metastases alone.

show abstract

Molecular determinants of photodynamic therapy for lung cancers

Abstract: Our translational research suggests that NPe6-PDT may be superior to Photofrin-PDT for the treatment of lung caner, and individualized approaches to PDT based on the expression status of Bcl-2 and/or BCRP may improve the efficacy of PDT in patients with lung cancers.

Cited by 12 publications

References 28 publications

Intraoperative Photodynamic Diagnosis Using Talaporfin Sodium Simultaneously Applied for Photodynamic Therapy against Malignant Glioma: A Prospective Clinical Study

Intraoperative Photodynamic Diagnosis Using Talaporfin Sodium Simultaneously Applied for Photodynamic Therapy against Malignant Glioma: A Prospective Clinical Study

Increased efficacy of photodynamic therapy via sequential targeting

Photodynamic therapy stimulates anti-tumor immune response in mouse models: the role of regulatory Tcells, anti-tumor antibodies, and immune attacks on brain metastases

Contact Info

Product

Resources

About