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Systemic photodynamic therapy with Fotolon® – A promising approach for tumor treatment – Not only for superficial lesions
Abstracts / Photodiagnosis and Photodynamic Therapy 17 (2017) A4–A78
bined with cryotherapy or laser ablation. Here we report one case of vulvar bowenoid papulosis that was successfully treated by combination PDT. A 31-year-old woman complained one-year history of vulvar discomfort. She had a history of vulvar condyloma acuminata 13 years ago and has been in remission since then. Visual examination showed that there were a few discrete brown and flat papules in the posterior commissure labiorum. Skin biopsy revealed multiple mitoses and marked pleomorphism in keratinocytes in all the epidermal layers. Polymerase chain reaction analysis of the lesion demonstrated the presence of high-risk HPV 16. The patient received ablative therapies prior to topical PDT. Briefly, first CO2 laser of 4 W was used to destroy the visible lesions, and then followed by four cycles of topical PDT mediated by aminolevulinic acid (ALA). 20% ALA (118 mg in 0.5 ml sterile water for injection, Shanghai Fudan Zhangjiang Bio-Pharmaceutical Co. Ltd.) was applied to the skin for 3-h before exposure to a light-emitting diode (LED) light source for 20 min. The interval between two sessions was 1–2 weeks. At present, the patient has no recurrence after 1year of follow-up. Such combined therapy has advantages in the treatment of vulvar bowenoid papulosis that include destroying both bulky lesions and subclinical infections [1–3]. References [1] C.H. Yang, J.C. Lee, C.H. Chen, C.Y. Hui, H.S. Hong, H.W. Kuo, Br. J. Dermatol. 149 (2003) 1297–1299. [2] X. Mi, W. Chai, H. Zheng, Y.G. Zuo, J. Li, Photodermatol. Photoimmunol. Photomed. 27 (2011) 176–180. [3] K. Chen, B.Z. Chang, M. Ju, X.H. Zhang, H. Gu, Br. J. Dermatol. 156 (2007) 516–520.
http://dx.doi.org/10.1016/j.pdpdt.2017.01.155 PDT in head and neck cancer Poster PH-068 Combination of photodynamic therapy and nimotuzumab inhibit tumor angiogenesis in an oral cancer xenograft model N.Q. Feng ∗ , R. Bhuvaneswari, T.S.P. Patricia, S.K. Chee National Cancer Centre, Singapore Aims: To investigate the mechanism of action involved in the treatment of oral squamous cell carcinoma (OSCC) with the combination of photodynamic therapy (PDT) and an anti-EGFR antibody, nimotuzumab. Methods: Effects of nimotuzumab on OSCC EGFR downstream signalling was analysed with flow cytometry and immunoblotting. Anti-angiogenic properties of nimotuzumab were studied by performing migration, invasion and tube formation assay on human umbilical vein endothelial cells (HUVEC). OSCC xenograft model in nude mice were treated with combination therapy of PDT and nimotuzumab, or with their individual mono-therapy, and tumor volume was monitored for a 14 days periodfrom thestart of the treatment. Tumor tissues were extracted at the end of the experiment. ELISA, immunoblotting and qPCR were employed to analyse the expression of various angiogenic markers and EGFR downstream signalling proteins from tumor lysates. Immunohistochemistry (IHC) of tumor tissue for CD31 vascular endothelial marker was used to verify the anti-angiogenic capacity of nimotuzumab on tumor tissue. Results: Nimotuzumab exhibits a significant dosage dependent inhibition of EGF-induced MAPK and AKT signalling in OSCC cells. Nimotuzumab reduced migration, invasion and tube formation ability of HUVEC. Combination therapy of PDT + nimotuzumab
A69
exhibited the greatest inhibition of tumor growth compared to their individual therapy alone. Combination therapy treated tumors had a lowered expression of angiogenic markers such as IL-6, IL-8 and MMP9. IHC with CD31 antibody revealed that tumor tissue had reduced vasculature following our combination therapy. Conclusion: Nimotuzumab can enhance the treatment efficacy of PDT by inhibiting tumor recurrence resulting from EGFR signalling and angiogenesis. http://dx.doi.org/10.1016/j.pdpdt.2017.01.156 Poster PH-069 ®
Systemic photodynamic therapy with Fotolon – A promising approach for tumor treatment – Not only for superficial lesions D. Hüttenberger 1,∗ , H. Sudhoff 2 , L. Freitag 3 , M. Haupt 1 1
Apocare Pharma GmbH, Bielefeld, Germany Klinikum Bielefeld, Bielefeld, Germany 3 Universitäts-spital Zürich, Zürich, Switzerland 2
The green porphyrin Chlorin e6 is known as a highly effective photosensitizer for systemic PDT. In a unique process of purification it is possible to produce a chlorin as a pure, highly water soluble ® sodium salt (Fotolon ), which was used for the following studies. Material and methods: In preclinical animal studies with healthy mice, tumor bearing mice and rats, the tissue distribution and depletion kinetics of Chlorin e6 and his photodynamic potential was monitored. The efficacy of enrichment and therapy was shown in some tumor models for lung and skin cancer entities. Clinical experiences: In some single cases in Otolaryngology (squamous cell carcinomas), gastroen-enterology (anal cancer) and in a clinical trial in pulmology (NSCLC), the photodynamic potential of Chlorin e6 was monitored in patients even with thicker lesions. Results: All trials were assisted by fluorescence spectroscopic methods and the Chlorin e6 level showed a selective enrichment in tumor tissues (up to 20:1) 3 h after i.v. application. In single case studies it was shown that the results were excellent. Even in tumors with wide stretched dimension the approach with PDT was successful. Tumors of over 1 cm depth and more than 10 cm width were treated successfully with serial approach. Conclusion: Chlorin e6 shows a high specific accumulation in neoplastic tissues. 3 h after application the fluorescence detection enables a calculation of an adequate photodynamic dose to realize an effective therapy. Because of a lack of drug related side effects and a rapid elimination over the hepatobilary system, a systemic ® photosensibility is uncommon. Depending on the tissue, Fotolon has, due to its excitation wavelength and the supply from the vascular system, a therapeutic active depth of up to 1.8 cm. In interstitial approaches and with series of therapies, the goal is a curative treatment of thicker tumor lesions. http://dx.doi.org/10.1016/j.pdpdt.2017.01.157
bined with cryotherapy or laser ablation. Here we report one case of vulvar bowenoid papulosis that was successfully treated by combination PDT. A 31-year-old woman complained one-year history of vulvar discomfort. She had a history of vulvar condyloma acuminata 13 years ago and has been in remission since then. Visual examination showed that there were a few discrete brown and flat papules in the posterior commissure labiorum. Skin biopsy revealed multiple mitoses and marked pleomorphism in keratinocytes in all the epidermal layers. Polymerase chain reaction analysis of the lesion demonstrated the presence of high-risk HPV 16. The patient received ablative therapies prior to topical PDT. Briefly, first CO2 laser of 4 W was used to destroy the visible lesions, and then followed by four cycles of topical PDT mediated by aminolevulinic acid (ALA). 20% ALA (118 mg in 0.5 ml sterile water for injection, Shanghai Fudan Zhangjiang Bio-Pharmaceutical Co. Ltd.) was applied to the skin for 3-h before exposure to a light-emitting diode (LED) light source for 20 min. The interval between two sessions was 1–2 weeks. At present, the patient has no recurrence after 1year of follow-up. Such combined therapy has advantages in the treatment of vulvar bowenoid papulosis that include destroying both bulky lesions and subclinical infections [1–3]. References [1] C.H. Yang, J.C. Lee, C.H. Chen, C.Y. Hui, H.S. Hong, H.W. Kuo, Br. J. Dermatol. 149 (2003) 1297–1299. [2] X. Mi, W. Chai, H. Zheng, Y.G. Zuo, J. Li, Photodermatol. Photoimmunol. Photomed. 27 (2011) 176–180. [3] K. Chen, B.Z. Chang, M. Ju, X.H. Zhang, H. Gu, Br. J. Dermatol. 156 (2007) 516–520.
http://dx.doi.org/10.1016/j.pdpdt.2017.01.155 PDT in head and neck cancer Poster PH-068 Combination of photodynamic therapy and nimotuzumab inhibit tumor angiogenesis in an oral cancer xenograft model N.Q. Feng ∗ , R. Bhuvaneswari, T.S.P. Patricia, S.K. Chee National Cancer Centre, Singapore Aims: To investigate the mechanism of action involved in the treatment of oral squamous cell carcinoma (OSCC) with the combination of photodynamic therapy (PDT) and an anti-EGFR antibody, nimotuzumab. Methods: Effects of nimotuzumab on OSCC EGFR downstream signalling was analysed with flow cytometry and immunoblotting. Anti-angiogenic properties of nimotuzumab were studied by performing migration, invasion and tube formation assay on human umbilical vein endothelial cells (HUVEC). OSCC xenograft model in nude mice were treated with combination therapy of PDT and nimotuzumab, or with their individual mono-therapy, and tumor volume was monitored for a 14 days periodfrom thestart of the treatment. Tumor tissues were extracted at the end of the experiment. ELISA, immunoblotting and qPCR were employed to analyse the expression of various angiogenic markers and EGFR downstream signalling proteins from tumor lysates. Immunohistochemistry (IHC) of tumor tissue for CD31 vascular endothelial marker was used to verify the anti-angiogenic capacity of nimotuzumab on tumor tissue. Results: Nimotuzumab exhibits a significant dosage dependent inhibition of EGF-induced MAPK and AKT signalling in OSCC cells. Nimotuzumab reduced migration, invasion and tube formation ability of HUVEC. Combination therapy of PDT + nimotuzumab
A69
exhibited the greatest inhibition of tumor growth compared to their individual therapy alone. Combination therapy treated tumors had a lowered expression of angiogenic markers such as IL-6, IL-8 and MMP9. IHC with CD31 antibody revealed that tumor tissue had reduced vasculature following our combination therapy. Conclusion: Nimotuzumab can enhance the treatment efficacy of PDT by inhibiting tumor recurrence resulting from EGFR signalling and angiogenesis. http://dx.doi.org/10.1016/j.pdpdt.2017.01.156 Poster PH-069 ®
Systemic photodynamic therapy with Fotolon – A promising approach for tumor treatment – Not only for superficial lesions D. Hüttenberger 1,∗ , H. Sudhoff 2 , L. Freitag 3 , M. Haupt 1 1
Apocare Pharma GmbH, Bielefeld, Germany Klinikum Bielefeld, Bielefeld, Germany 3 Universitäts-spital Zürich, Zürich, Switzerland 2
The green porphyrin Chlorin e6 is known as a highly effective photosensitizer for systemic PDT. In a unique process of purification it is possible to produce a chlorin as a pure, highly water soluble ® sodium salt (Fotolon ), which was used for the following studies. Material and methods: In preclinical animal studies with healthy mice, tumor bearing mice and rats, the tissue distribution and depletion kinetics of Chlorin e6 and his photodynamic potential was monitored. The efficacy of enrichment and therapy was shown in some tumor models for lung and skin cancer entities. Clinical experiences: In some single cases in Otolaryngology (squamous cell carcinomas), gastroen-enterology (anal cancer) and in a clinical trial in pulmology (NSCLC), the photodynamic potential of Chlorin e6 was monitored in patients even with thicker lesions. Results: All trials were assisted by fluorescence spectroscopic methods and the Chlorin e6 level showed a selective enrichment in tumor tissues (up to 20:1) 3 h after i.v. application. In single case studies it was shown that the results were excellent. Even in tumors with wide stretched dimension the approach with PDT was successful. Tumors of over 1 cm depth and more than 10 cm width were treated successfully with serial approach. Conclusion: Chlorin e6 shows a high specific accumulation in neoplastic tissues. 3 h after application the fluorescence detection enables a calculation of an adequate photodynamic dose to realize an effective therapy. Because of a lack of drug related side effects and a rapid elimination over the hepatobilary system, a systemic ® photosensibility is uncommon. Depending on the tissue, Fotolon has, due to its excitation wavelength and the supply from the vascular system, a therapeutic active depth of up to 1.8 cm. In interstitial approaches and with series of therapies, the goal is a curative treatment of thicker tumor lesions. http://dx.doi.org/10.1016/j.pdpdt.2017.01.157