Photodynamic therapy: Combined modality approaches targeting the tumor microenvironment

Gomer, Charles J.; Ferrario, Angela; Luna, Marian; Rucker, Natalie; Wong, Sam

doi:10.1002/lsm.20339

Cited by 140 publications

(142 citation statements)

References 37 publications

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“…The excited photosensitizer interacts with molecular oxygen and results in the production of ROS, which can lead to damage of the cellular constituents and subsequent cell destruction (12)(13)(14). It is believed that ROS plays a direct role in damaging cells subjected to PDT (2,4). Therefore, we examined intracellular ROS production by Ce 6 -PDT in the RK3E-ras cells.…”

Section: Resultsmentioning

confidence: 99%

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Efficient preparation of highly pure chlorin e6 and its photodynamic anti-cancer activity in a rat tumor model

Ahn¹

2009

Oncol Rep

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Abstract. Photodynamic therapy (PDT) is currently being used as an alternative therapeutic modality for a variety of malignant tumors. This study was performed to show an efficient preparation of second generation of photosensitizer chlorin e 6 (Ce 6 ) with high yield and purity, and to test antitumor activity of Ce 6 -induced PDT (Ce 6 -PDT) both in vitro and in vivo using a rat tumor model. Three-week-old male Sprague-Dawley (SD) rats were inoculated s.c. on the right flank with 5x10 6 RK3E-ras cells. The animals were administered i.v. with Ce 6 (10 mg/kg) and 24 h later, PDT was performed using a laser diode at a light dose of 100 J/cm 2 . Ce 6 -PDT generated reactive oxygen species and led to significant growth inhibition in RK3E-ras cell. In addition, Ce 6 -PDT induced apoptosis through the activation of caspase-3 and its downstream target, PARP cleavage. The protein level of antiapoptotic bcl-2 was also reduced by Ce 6 -PDT in RK3E-ras cells. In in vivo experiments, application of Ce 6 -PDT led to a significant reduction of tumor size. PCNA immunostaining and TUNEL assay revealed that Ce 6 -PDT inhibited tumor cell proliferation and increased apoptosis. These findings suggest that the newly purified Ce 6 -PDT can effectively arrest tumor growth by inhibiting cell proliferation and inducing apoptosis.

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Section: Resultsmentioning

confidence: 99%

“…During light exposure, photosensitizers that are localized in mitochondria may induce apoptosis, while those localized in lysosomes and cell membranes may cause necrosis. Apoptosis is responsible for PDT-mediated tumor cell death in vitro and tumor ablation in vivo (2,4).…”

Section: Introductionmentioning

confidence: 99%

Efficient preparation of highly pure chlorin e6 and its photodynamic anti-cancer activity in a rat tumor model

Ahn¹

2009

Oncol Rep

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“…PDT has a direct cytotoxic effect and an indirect effect on the tumor microenvironment, 40 and rapidly induces apoptosis, an inflammatory reaction, tumor-specific and/or non-specific immune reactions and damages the tumor bed microvasculature. [40][41][42] An enhanced apoptotic response, as evidenced by the high Bax to Bcl-2 protein ratio in LLC-IL-6 cells, and IL-6 expression are important determinants of the antitumor effect of PDT. 43 A synergic cytotoxic effect by a cytokine or genetic alterations induced by the anticancer drugs might promote the PDT effect.…”

Section: Discussionmentioning

confidence: 99%

Synergic effect of photodynamic therapy using talaporfin sodium with conventional anticancer chemotherapy for the treatment of bile duct carcinoma

Nonaka¹,

Nanashima²,

Nonaka³

et al. 2013

Journal of Surgical Research

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“…PDT induces the photochemical generation of cytotoxic reactive oxygen species within the irradiated tissue, which leads to tumor cell death through necrosis, apoptosis, and/ or autophagy (4)(5)(6)(7). Vascular injury, tissue hypoxia, and inflammatory reactions with concomitant expression of growth factors, matrix metalloproteinases, cytokines, and prostaglandins are observed within the treated tumor microenvironment (8)(9)(10)(11)(12). These treatment-related reactions can be associated with an angiogenic and/or survival phenotype that may play a role in tumor recurrences following PDT and highlight the need to more fully understand the molecular responses initiated by PDT.…”

Section: Introductionmentioning

confidence: 99%

Survivin, a Member of the Inhibitor of Apoptosis Family, Is Induced by Photodynamic Therapy and Is a Target for Improving Treatment Response

et al. 2007

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We observed that photodynamic therapy (PDT) induces the expression and phosphorylation of the inhibitor of apoptosis (IAP) protein survivin in murine and human cancer cells and tumors. Survivin inhibits caspase-9, blocks apoptosis, and is associated with resistance to chemotherapy and radiation. Survivin is a client protein for the 90-kDa heat shock protein (Hsp-90), and the binding of survivin to Hsp-90 assists in the maturation, proper folding, assembly, and transport of this IAP protein. A derivative of the antibiotic geldanamycin, 17-allylamino-17-demethoxygeldanamycin (17-AAG), interferes with proper binding of client proteins, such as survivin, to Hsp-90 and leads to misfolding of client proteins, ubiquination, and proteasome degradation. We hypothesized that PDT efficacy may be reduced by treatment-mediated expression and phosphorylation of survivin, and therefore, targeting the survivin pathway could increase PDT responsiveness. To address this hypothesis, we examined cellular and molecular responses following exposure to PDT, 17-AAG, and the combination of PDT plus 17-AAG in human BT-474 breast cancer cells using Photofrin and NPe6 as photosensitizers. Cells treated with the combination of PDT and 17-AAG exhibited decreased expression of the Hsp-90 client proteins phosphorylated survivin, phosphorylated Akt, and Bcl-2. The decreased expression of these client proteins was accompanied by higher apoptotic indexes and increased cytotoxicity. To confirm a specific role for survivin in modulating PDT, we used a human melanoma cell line, YUSAC2/T34A-C4, stably transfected with an inducible dominant-negative survivin gene under the control of a tetracycline-regulated (tet-off) promoter. PDT treatment of melanoma cells expressing the dominant-negative survivin resulted in increased cleavage of the caspase substrate poly(ADP-ribose) polymerase, apoptosis, and cytotoxicity when compared with results following PDT of the same melanoma cell line expressing wild-type survivin. These results show for the first time that targeting survivin and possibly other Hsp-90 client proteins improves in vitro PDT responsiveness and suggest that manipulation of the antiapoptotic pathway maintained by survivin may enhance PDTmediated cancer therapy. [Cancer Res 2007;67(10):4989-95]

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Photodynamic therapy: Combined modality approaches targeting the tumor microenvironment

Abstract: Improvements in PDT tumor responsiveness may be achieved by employing combined modality regimens targeting malignant cells as well as treatment-induced angiogenesis and/or inflammation.

Cited by 140 publications

References 37 publications

Efficient preparation of highly pure chlorin e6 and its photodynamic anti-cancer activity in a rat tumor model

Efficient preparation of highly pure chlorin e6 and its photodynamic anti-cancer activity in a rat tumor model

Synergic effect of photodynamic therapy using talaporfin sodium with conventional anticancer chemotherapy for the treatment of bile duct carcinoma

Survivin, a Member of the Inhibitor of Apoptosis Family, Is Induced by Photodynamic Therapy and Is a Target for Improving Treatment Response

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