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Photodynamic therapy for gynecological diseases and breast cancer.

Shishkova N, Kuznetsova O, Berezov T - Cancer Biol Med (2012)

Bottom Line: Cytotoxic reactive oxygen species (ROS) are generated by the tissue-localized non-toxic sensitizer upon illumination and in the presence of oxygen.The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence.The article also highlights the clinical responses to PDT, and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Medicine, People's Friendship University of Russia, Moscow 117198, Russia.

ABSTRACT
Photodynamic therapy (PDT) is a minimally invasive and promising new method in cancer treatment. Cytotoxic reactive oxygen species (ROS) are generated by the tissue-localized non-toxic sensitizer upon illumination and in the presence of oxygen. Thus, selective destruction of a targeted tumor may be achieved. Compared with traditional cancer treatment, PDI has advantages including higher selectivity and lower rate of toxicity. The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence. This article reviews previous studies done on PDT treatment and photodetection of cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, ovarian and breast cancer, and PDT application in treating non-cancer lesions. The article also highlights the clinical responses to PDT, and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy.

No MeSH data available.


Related in: MedlinePlus

Photodynamic therapy mechanism, as explained in detail in the text.
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f1: Photodynamic therapy mechanism, as explained in detail in the text.

Mentions: Photodynamic therapy (PDT) is a mode of therapy used in cancer treatment where drug activity is locally controlled by light (Figure 1). The ground state non-toxic photosensitizer achieves a higher unstable energy state (singlet state) upon illumination with an appropriate light wavelength and in the presence of oxygen. In this unstable state, the activated photosensitizer releases energy either by emitting heat and light or by the conversion of the unstable state into an intermediate energy state (triplet state) before returning to the stable ground state. In the triplet state, the photosensitizer generates reactive oxygen species (ROS), such as superoxide and hydroxyl radicals or singlet oxygen. ROS rapidly reacts with biological substrates, which initiates an apoptotic or necrotic response. This process eventually leads to oxidative damage and cell death. The intracellular localization of the photosensitizer activity is of great importance because mitochondrial damage generally leads to apoptosis, whereas plasma membrane damage induces necrosis [1-3]. Photofrin, one of the most widely used photosensitizers, is localized in the mitochondria due to its hydrophobicity and its affinity to the binding site on the mitochondrial membrane [4]. A frequently used drug in PDT is 5-aminolaevulinic acid (ALA). However, 5-ALA is not a photosensitizer, but a precursor of the endogenous photosensitizer protoporphyrin IX, which is a member of the heme synthesis pathway that occurs in the mitochondria [5]. PDT affects the tumor vasculature, where illumination and ROS production cause vessel shutdown and lead to tumor hypoxia [6]. PDT also affects the immune system [7, 8]. The tissue selectivity of different photosensitizers is currently under investigation. Moreover, the laser irradiation restricted within the lesion area combined with the short lifespan of the emerging cytotoxic species ensures that phototoxic damage is mainly localized in the lesion with minimal inclusion of the surrounding tissues. The application mode of photosensitizers may be topical or systemic (oral or intravenous). Indications for PDT include cancers where the entire lesion is visible through an endoscope to enable laser irradiation. PDT has been applied for the treatment of skin cancer, surperficial esophageal cancer, lung cancer, and gastric cancer [9, 10]. In addition, bladder and prostate cancers have been treated with PDT [11–13]. In this review, PDT effectiveness in treating gynecological cancers, such as ovarian cancer, cervical intraepithelial neoplasia (CIN), and vulvar intraepithelial neoplasia (VIN) is discussed. The available data on targeted and non-targeted treatment modes for breast cancer is also summarized.


Photodynamic therapy for gynecological diseases and breast cancer.

Shishkova N, Kuznetsova O, Berezov T - Cancer Biol Med (2012)

Photodynamic therapy mechanism, as explained in detail in the text.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643637&req=5

f1: Photodynamic therapy mechanism, as explained in detail in the text.
Mentions: Photodynamic therapy (PDT) is a mode of therapy used in cancer treatment where drug activity is locally controlled by light (Figure 1). The ground state non-toxic photosensitizer achieves a higher unstable energy state (singlet state) upon illumination with an appropriate light wavelength and in the presence of oxygen. In this unstable state, the activated photosensitizer releases energy either by emitting heat and light or by the conversion of the unstable state into an intermediate energy state (triplet state) before returning to the stable ground state. In the triplet state, the photosensitizer generates reactive oxygen species (ROS), such as superoxide and hydroxyl radicals or singlet oxygen. ROS rapidly reacts with biological substrates, which initiates an apoptotic or necrotic response. This process eventually leads to oxidative damage and cell death. The intracellular localization of the photosensitizer activity is of great importance because mitochondrial damage generally leads to apoptosis, whereas plasma membrane damage induces necrosis [1-3]. Photofrin, one of the most widely used photosensitizers, is localized in the mitochondria due to its hydrophobicity and its affinity to the binding site on the mitochondrial membrane [4]. A frequently used drug in PDT is 5-aminolaevulinic acid (ALA). However, 5-ALA is not a photosensitizer, but a precursor of the endogenous photosensitizer protoporphyrin IX, which is a member of the heme synthesis pathway that occurs in the mitochondria [5]. PDT affects the tumor vasculature, where illumination and ROS production cause vessel shutdown and lead to tumor hypoxia [6]. PDT also affects the immune system [7, 8]. The tissue selectivity of different photosensitizers is currently under investigation. Moreover, the laser irradiation restricted within the lesion area combined with the short lifespan of the emerging cytotoxic species ensures that phototoxic damage is mainly localized in the lesion with minimal inclusion of the surrounding tissues. The application mode of photosensitizers may be topical or systemic (oral or intravenous). Indications for PDT include cancers where the entire lesion is visible through an endoscope to enable laser irradiation. PDT has been applied for the treatment of skin cancer, surperficial esophageal cancer, lung cancer, and gastric cancer [9, 10]. In addition, bladder and prostate cancers have been treated with PDT [11–13]. In this review, PDT effectiveness in treating gynecological cancers, such as ovarian cancer, cervical intraepithelial neoplasia (CIN), and vulvar intraepithelial neoplasia (VIN) is discussed. The available data on targeted and non-targeted treatment modes for breast cancer is also summarized.

Bottom Line: Cytotoxic reactive oxygen species (ROS) are generated by the tissue-localized non-toxic sensitizer upon illumination and in the presence of oxygen.The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence.The article also highlights the clinical responses to PDT, and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, School of Medicine, People's Friendship University of Russia, Moscow 117198, Russia.

ABSTRACT
Photodynamic therapy (PDT) is a minimally invasive and promising new method in cancer treatment. Cytotoxic reactive oxygen species (ROS) are generated by the tissue-localized non-toxic sensitizer upon illumination and in the presence of oxygen. Thus, selective destruction of a targeted tumor may be achieved. Compared with traditional cancer treatment, PDI has advantages including higher selectivity and lower rate of toxicity. The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence. This article reviews previous studies done on PDT treatment and photodetection of cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, ovarian and breast cancer, and PDT application in treating non-cancer lesions. The article also highlights the clinical responses to PDT, and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy.

No MeSH data available.


Related in: MedlinePlus