Öz
Kanser,
tüm dünyada olduğu gibi ülkemizde de en ölümcül hastalıkların başında
gelmektedir. Kanserin, lokal, minimum yan etkiyle ve hedefe yönelik olarak
tedavisi hasta için büyük önem taşımaktadır. Fotodinamik Terapi (FDT), lokal,
fotokimyaya dayalı ve yan etkisi minimum olan bir tedavi yöntemidir. Özetle
FDT, ışıkla aktive olan ilaç (fotosensitizer), ışık ve oksijenin birleşmesi
sonucu ortaya çıkan serbest radikallerin ve/veya tekil (singlet) oksijenin
hücrede bir dizi zincir reaksiyon başlatarak hücre ölümüne sebep olması
prensibine dayanır. Oksijen, ışık ve fotosensitizer
tek başına herhangi bir toksik etki göstermeyip, ancak bir araya geldiklerinde
başlayan fotokimyasal reaksiyonlar sonucu oluşan sitotoksisite sebebiyle
hedeflenen hücrenin ölümü gerçekleşir.
FDT’nin en önemli bileşeni hücre içinde, ışık enerjisini kimyasal
enerjiye dönüştüren araç olan fotosensitizerdir. FDT’nin etkinliği farklı terapi modelleri ile birleştirilerek
arttırılabilir. Kanser
gibi dejeneratif hastalıkların genellikle birden fazla patolojik mekanizma
içerdiklerini ve bu hastalıklarla tek tedavi yöntemiyle savaşmanın yeterli
olmayacağını akılda tutmak gerekir. Bu nedenle iki ya da daha fazla
tedavi yönteminin eş zamanlı olarak kullanılması başarıyı arttırmaktadır. Kombinasyon terapinin
amacı kullanılan tedavi yöntemleri ve/veya ilaç ile hücredeki farklı sinyal
yolaklarını dolayısı ile farklı hücre hasarı yollarını hedef alarak birden
fazla mekanizmayı aktive ederek kanser hücresinin yok edilmesi ihtimalini
arttırmaktır. Bu bilgilerin ışığında FDT
ve kemoterapiden oluşan yeni kombinasyon terapinin SKOV-3 over kanser hücre
hattında etkisi araştırıldı. Özgün, suda
çözünürlüğü yüksek fotosensitizer ile klinikte sıklıkla kemoterapi ilacı olarak
kullanılan İrinotekan kullanıldı. FDT ve
kemoterapiden oluşan kombinasyon terapinin uygulanan tedavinin sırasına bağlı
olarak çok büyük değişiklik gösterdiği görüldü.
Örneğin, FDT’nin önce uygulandığı durumda belirli ilaç dozlarında güçlü
antagonist etki görüldü. Öte yandan,
aynı ilaç konsantrasyonlarında yalnızca uygulama sırası değiştirilerek sinerjik
etkinin elde edilebileceği görüldü.
Anahtar Kelimeler
Fotodinamik Terapi over kanseri SKOV-3 kombinasyon terapi toksisite ROS Irinotekan
Kaynakça
- Who Healty Organization (February, 2017). Cancer. http://www.who.int/mediacentre/factsheets/fs297/en/ . 12 Haziran 2017 tarihinde erişildi.
- Başaran, B. B., C. Güler, Z. Eryılmaz, G. K. Yentur ve E. Pulgat (2012). T.C. Sağlık Bakanlığı İstatistikleri Yıllığı. Ankara: T. C. Sağlık Bakanlığı.
- Mir, Y., Elrington, S. A., & Hasan, T. (2013). A new nanoconstruct for epidermal growth factor receptor-targeted photo-immunotherapy of ovarian cancer. Nanomedicine: Nanotechnology, Biology and Medicine, 9(7), 1114-1122.
- Postiglione, I., Chiaviello, A., Palumbo, G. (2011) "Enhancing Photodynamic Therapy Efficacy by Combination Therapy: Dated, Current and Oncoming Strategies." Cancers 3(2), 2597-2629.
- Wilson, B. C., & Patterson, M. S. (2008). The physics, biophysics and technology of photodynamic therapy. Physics in medicine and biology, 53(9), R61.
- Zheng H. (2005) A Review of Progress in Clinical Photodynamic Therapy. Technology in Cancer Research and Treatment, 4, 283.
- http://www.moderncancerhospital.com/cancer-treatments/photodynamic-therapy/ Türkçeleştirilmiştir. 26 Haziran 2017 tarihinde erişildi
- Yano, S., Hirohara, S., Obata, M., Hagiya, Y., Ogura, S. I., Ikeda, A., and John, T. (2011). Current states and future views in photodynamic therapy. Journal of Photochemistry and Photobiology C: Photochemistry Reviews, 12(1), 46-67.
- Castano, A. P., Mroz, P., & Hamblin, M. R. (2006). Photodynamic therapy and anti-tumour immunity. Nature Reviews Cancer, 6(7), 535-545.
- Moan, J., Berg, K. (1991) The photodegradation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen. Photochemistry and Photobiology, 53,549–53.
- Hahn, S. M., Putt, M. E., Metz, J., Shin, D. B., Rickter, E., Menon, C., ... & Busch, T. M. (2006). Photofrin uptake in the tumor and normal tissues of patients receiving intraperitoneal photodynamic therapy. Clinical Cancer Research, 12(18), 5464-5470.
- DeLaney, T. F., Smith, P. D., Thomas, G. F., Tochnen, Z. A., Sindelar, W. F., Pass, H. I., and Mitchell, J. B. (1991). A light-diffusing device for intraoperative photodynamic therapy in the peritoneal or pleural cavity. Journal of clinical laser medicine & surgery, 9(5), 361-366.
- Hendren, S.K., Hahn, S.M., Spitz, F.R., Bauer, T.W., Rubin, S.C., Zhu, T., et al. (2001). Phase II trial of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. Ann Surg Oncol 8, 65 – 71.
- Wierrani, F., Fiedler, D., Grin, W., Henry, M., Dienes, E., Gharehbaghi, K., & Grünberger, W. (1997). Clinical effect of meso‐tetrahydroxyphenylchlorine based photodynamic therapy in recurrent carcinoma of the ovary: preliminary results. BJOG: An International Journal of Obstetrics & Gynaecology, 104(3), 376-378.
- Goff, B.A., Blake, J., Bamberg, M.P., Hasan T. (1996). Treatment of ovarian cancer with photodynamic therapy and immunoconjugates in a murine ovarian cancer. British Journal of Cancer, 74, 1194-1198.
- Rizvi, I., Celli, J.P., Evans, C. L., Abu-Yousif, A.Y., Muzikansky, A., Pogue, B.P., Finkelstein, D., and Hasan, T. (2010). “Synergistic Enhancement of Carboplatin Efficacy with Photodynamic Therapy in a Three-dimensional Model for Micrometastatic Ovarian Cancer” Cancer Research, 15, 70, 22, 9319–9328
- Kim, Y.W., Bae, S.M., Battogtokh, G., Bang, H.J., Ahn, W.S. (2012) "Synergistic anti-tumor effects of combination of photodynamic therapy and arsenic compound in cervical cancer cells: in vivo and in vitro studies." PLOS One 7 (6):e38583
- Wei, X.Q., Ma, H.Q., Liu, A.H., Zhang Y.Z. (2013) "Synergistic anticancer activity of 5-aminolevulinic acid photodynamic therapy in combination with low-dose cisplatin on Hela cells." Asian Pacific Journal of Cancer Prevention 14 (5), 3023-8.
- Erdem, S. S., Parlar, E. R., Obeidin, V. A. ve Şahin, U. (2017) Skov-3 over kanseri hücre hattında fotodinamik terapi uygulaması. Haydarpaşa Numune Eğitim Araştırma Hastanesi Tıp Dergisi, basım aşamasında
- Chou, T.C., and Talalay, P. (1984) Quantitative analysis of dose effect relationship: The combined effects of multiple drugs on enzyme inhibitors. Adv. Enzyme Regul, 22, 27-55
Öz
Cancer is one of the most
leading causes of death in Turkey as well as in the world. It is very critical
to cure the cancer via targeted therapy that is locally applied and shows minimum
side effects for patient’s life quality.
Photodynamic therapy (PDT) is a local, photochemistry based treatment,
which has minimum side effects. In
brief, PDT is a result of a combination of photosensitizer, a drug that is
activated by light, light and oxygen that generates free radicals and/or
singlet oxygen and starts series of reactions in cell and eventually cause cell
death. While light, oxygen and photosensitizer has no cytotoxic effect alone,
combination of three starts all photochemical reactions and as a result
cytotoxicity is generated in the tissue. Photosensitizer, converting light
energy to the chemical energy in the cell, is the most critical component of
PDT. One way to improve effectiveness of PDT is to combine it with different
treatment modalities. Cancer and other degenerative diseases involve several pathological
mechanisms and require multiple treatment methods such as combination
therapies. A combination therapy targets to bring together current therapies
and/or drugs to act upon different cellular signaling pathways/ cell damage
pathways thus activating various mechanisms in the cell increasing the success
rate of the treatment. In the light of
these information, a new combination
therapy, based on PDT and chemotherapy, has been investigated towards SKOV-3
over cancer cell line. A novel and
water-soluble photosensitizer and a chemotherapy drug called Irinotecan that is
been used in clinic were employed. Our
results showed that outcome of the combination therapy, which is composed of
PDT and chemotherapy, highly depends on the order of the treatment. For
instance, when PDT applied first, strong antagonism is observed at certain drug
concentrations. On the other hand, synergism is observed using the same drug
concentrations yet by only changing the order of the treatment.
Anahtar Kelimeler
Photodynamic Therapy SKOV-3 combination therapy photosensitizer toxicity ROS ovarian cancer Irinotecan
Kaynakça
- Who Healty Organization (February, 2017). Cancer. http://www.who.int/mediacentre/factsheets/fs297/en/ . 12 Haziran 2017 tarihinde erişildi.
- Başaran, B. B., C. Güler, Z. Eryılmaz, G. K. Yentur ve E. Pulgat (2012). T.C. Sağlık Bakanlığı İstatistikleri Yıllığı. Ankara: T. C. Sağlık Bakanlığı.
- Mir, Y., Elrington, S. A., & Hasan, T. (2013). A new nanoconstruct for epidermal growth factor receptor-targeted photo-immunotherapy of ovarian cancer. Nanomedicine: Nanotechnology, Biology and Medicine, 9(7), 1114-1122.
- Postiglione, I., Chiaviello, A., Palumbo, G. (2011) "Enhancing Photodynamic Therapy Efficacy by Combination Therapy: Dated, Current and Oncoming Strategies." Cancers 3(2), 2597-2629.
- Wilson, B. C., & Patterson, M. S. (2008). The physics, biophysics and technology of photodynamic therapy. Physics in medicine and biology, 53(9), R61.
- Zheng H. (2005) A Review of Progress in Clinical Photodynamic Therapy. Technology in Cancer Research and Treatment, 4, 283.
- http://www.moderncancerhospital.com/cancer-treatments/photodynamic-therapy/ Türkçeleştirilmiştir. 26 Haziran 2017 tarihinde erişildi
- Yano, S., Hirohara, S., Obata, M., Hagiya, Y., Ogura, S. I., Ikeda, A., and John, T. (2011). Current states and future views in photodynamic therapy. Journal of Photochemistry and Photobiology C: Photochemistry Reviews, 12(1), 46-67.
- Castano, A. P., Mroz, P., & Hamblin, M. R. (2006). Photodynamic therapy and anti-tumour immunity. Nature Reviews Cancer, 6(7), 535-545.
- Moan, J., Berg, K. (1991) The photodegradation of porphyrins in cells can be used to estimate the lifetime of singlet oxygen. Photochemistry and Photobiology, 53,549–53.
- Hahn, S. M., Putt, M. E., Metz, J., Shin, D. B., Rickter, E., Menon, C., ... & Busch, T. M. (2006). Photofrin uptake in the tumor and normal tissues of patients receiving intraperitoneal photodynamic therapy. Clinical Cancer Research, 12(18), 5464-5470.
- DeLaney, T. F., Smith, P. D., Thomas, G. F., Tochnen, Z. A., Sindelar, W. F., Pass, H. I., and Mitchell, J. B. (1991). A light-diffusing device for intraoperative photodynamic therapy in the peritoneal or pleural cavity. Journal of clinical laser medicine & surgery, 9(5), 361-366.
- Hendren, S.K., Hahn, S.M., Spitz, F.R., Bauer, T.W., Rubin, S.C., Zhu, T., et al. (2001). Phase II trial of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors. Ann Surg Oncol 8, 65 – 71.
- Wierrani, F., Fiedler, D., Grin, W., Henry, M., Dienes, E., Gharehbaghi, K., & Grünberger, W. (1997). Clinical effect of meso‐tetrahydroxyphenylchlorine based photodynamic therapy in recurrent carcinoma of the ovary: preliminary results. BJOG: An International Journal of Obstetrics & Gynaecology, 104(3), 376-378.
- Goff, B.A., Blake, J., Bamberg, M.P., Hasan T. (1996). Treatment of ovarian cancer with photodynamic therapy and immunoconjugates in a murine ovarian cancer. British Journal of Cancer, 74, 1194-1198.
- Rizvi, I., Celli, J.P., Evans, C. L., Abu-Yousif, A.Y., Muzikansky, A., Pogue, B.P., Finkelstein, D., and Hasan, T. (2010). “Synergistic Enhancement of Carboplatin Efficacy with Photodynamic Therapy in a Three-dimensional Model for Micrometastatic Ovarian Cancer” Cancer Research, 15, 70, 22, 9319–9328
- Kim, Y.W., Bae, S.M., Battogtokh, G., Bang, H.J., Ahn, W.S. (2012) "Synergistic anti-tumor effects of combination of photodynamic therapy and arsenic compound in cervical cancer cells: in vivo and in vitro studies." PLOS One 7 (6):e38583
- Wei, X.Q., Ma, H.Q., Liu, A.H., Zhang Y.Z. (2013) "Synergistic anticancer activity of 5-aminolevulinic acid photodynamic therapy in combination with low-dose cisplatin on Hela cells." Asian Pacific Journal of Cancer Prevention 14 (5), 3023-8.
- Erdem, S. S., Parlar, E. R., Obeidin, V. A. ve Şahin, U. (2017) Skov-3 over kanseri hücre hattında fotodinamik terapi uygulaması. Haydarpaşa Numune Eğitim Araştırma Hastanesi Tıp Dergisi, basım aşamasında
- Chou, T.C., and Talalay, P. (1984) Quantitative analysis of dose effect relationship: The combined effects of multiple drugs on enzyme inhibitors. Adv. Enzyme Regul, 22, 27-55
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Sağlık Kurumları Yönetimi |
| Bölüm | Orjinal Araştırma |
| Yazarlar | |
| Yayımlanma Tarihi | 5 Mart 2018 |
| Yayımlandığı Sayı | Yıl 2018 Cilt: 49 Sayı: 1 |
