Efficacy and safety of photodynamic therapy for cervical intraepithelial neoplasia and human papilloma virus infection

Zhang, Wenjia; Zhang, Aijia; Sun, Wenhui; Yue, Ying; Li, Hong

doi:10.1097/md.0000000000010864

Cited by 59 publications

(49 citation statements)

References 35 publications

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“…However, there is an urgent need to develop effective approaches to treat peritoneal carcinosis of ovarian origin. Photodynamic therapy (PDT) has been used in many areas, including the treatment of cutaneous and pleural diseases [9]. In fact, several clinical trials have detailed the use of this therapy in skin cancer [10] or Glioblastoma [11].…”

Section: Introductionmentioning

confidence: 99%

Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

Baydoun

Moralès

Frochot

et al. 2020

JCM

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Often discovered at an advanced stage, ovarian cancer progresses to peritoneal carcinoma, which corresponds to the invasion of the serosa by multiple tumor implants. The current treatment is based on the combination of chemotherapy and tumor cytoreduction surgery. Despite the progress and standardization of surgical techniques combined with effective chemotherapy, post-treatment recurrences affect more than 60% of women in remission. Photodynamic therapy (PDT) has been particularly indicated for the treatment of superficial lesions on large surfaces and appears to be a relevant candidate for the treatment of microscopic intraperitoneal lesions and non-visible lesions. However, the impact of this therapy on immune cells remains unclear. Hence, the objective of this study is to validate the efficacy of a new photosensitizer [pyropheophorbide a-polyethylene glycol-folic acid (PS)] on human ovarian cancer cells and to assess the impact of the secretome of PDT-treated cells on human peripheral blood mononuclear cells (PBMC). We show that PS, upon illumination, can induce cell death of different ovarian tumor cells. Furthermore, PDT using this new PS seems to favor activation of the immune response by inducing the secretion of effective cytokines and inhibiting the pro-inflammatory and immunosuppressive ones, as well as releasing extracellular vesicles (EVs) prone to activating immune cells. Finally, we show that PDT can activate CD4+ and CD8+ T cells, resulting in a potential immunostimulating process. The results of this pilot study therefore indicate that PS-PDT treatment may not only be effective in rapidly and directly destroying target tumor cells but also promote the activation of an effective immune response; notably, by EVs. These data thus open up good prospects for the treatment of micrometastases of intraperitoneal ovarian carcinosis which are currently inoperable.

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Section: Introductionmentioning

confidence: 99%

Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

Baydoun

Moralès

Frochot

et al. 2020

JCM

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“…PS photoactivation is a well-established therapeutic approach used to promote cell killing based on the interaction between visible light and matter [1,2]. The use of PS drugs in the clinic is termed “photodynamic therapy” (PDT), which is successfully targeted to cutaneous cancers, infections, and other pathologies [3,4,5,6,7]. In PDT, wavelength-selective light exposure of cells loaded with a PS promotes the inert PS molecule to a relatively long-lived excited state in which it interacts with molecular oxygen (O 2 ).…”

Section: Introductionmentioning

confidence: 99%

Photosensitizer Activation Drives Apoptosis by Interorganellar Ca2+ Transfer and Superoxide Production in Bystander Cancer Cells

Nardin

Peres

Mazzarda

et al. 2019

Cells

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In cells, photosensitizer (PS) activation by visible light irradiation triggers reactive oxygen species (ROS) formation, followed by a cascade of cellular responses involving calcium (Ca2+) and other second messengers, resulting in cell demise. Cytotoxic effects spread to nearby cells not exposed to light by poorly characterized so-called “bystander effects”. To elucidate the mechanisms involved in bystander cell death, we used both genetically encoded biosensors and fluorescent dyes. In particular, we monitored the kinetics of interorganellar Ca2+ transfer and the production of mitochondrial superoxide anion (O2−∙) and hydrogen peroxide (H2O2) in irradiated and bystander B16-F10 mouse melanoma cancer cells. We determined that focal PS photoactivation in a single cell triggers Ca2+ release from the endoplasmic reticulum (ER) also in the surrounding nonexposed cells, paralleled by mitochondrial Ca2+ uptake. Efficient Ca2+ efflux from the ER was required to promote mitochondrial O2−∙ production in these bystander cells. Our results support a key role for ER–mitochondria communication in the induction of ROS-mediated apoptosis in both direct and indirect photodynamical cancer cell killing.

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“…The complete remission of lesions totalized 57.14%, of which 21.43% presented at the follow up of one year and 35.71%at two years. In a systematic review and meta-analysis by Zhang et al, they concluded that PDT showed more significant results in eradicating premalignant lesions (282 patients) than the placebo group (141 patients) [15].…”

Section: Resultsmentioning

confidence: 99%

“…In this study we were also able to follow 14 patients for two years from the placebo group, where eight received only irradiation at 80 J/cm 2 and six patients received only cream containing 20% Methyl aminolevulinate (MAL) in the cervix for one hour. It seems to be a low number of patients in the placebo group, but other authors who work in gynecological PDT and also in the treatment of low- and high-grade CIN report that their placebo groups are in a smaller number than the treatment group and it is known that a significant difference between these two groups is not expected, especially for CIN 1 treatment once most of CIN 1 lesions disappear naturally [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…The alarming statistics of cervical cancer in Brazil led us to start a new clinical project focused on this need. Therefore, in 2012, a new device was developed (CerCa 150 System ® , MMOptics, São Carlos-SP, Brazil) and in 2013, a new clinical trial was initiated [15], with as a principal goal the prevention of cervical cancer by an early cost-efficient treatment of cervical intraepithelial neoplasia.…”

Section: Introductionmentioning

confidence: 99%

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Long Term Effectiveness of Photodynamic Therapy for CIN Treatment

Inada

Buzzá

Leite³

et al. 2019

Pharmaceuticals

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(1) Background: Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in women worldwide. The highest incidence rates are in Africa, followed by South-Central Asia and South America. According to the Brazilian National Institute of Cancer (INCA), 16,370 new cases of cervical cancer were estimated for each year of the biennium of 2018–2019. About 90% of cervical cancers originate from the malignant progression of cervical intraepithelial neoplasia (CIN) which is classified based on cytohistological characteristics (low- and high-grade lesions). The present study reports the long-term effectiveness of topical photodynamic therapy (PDT) for CIN grades 1 and 2/3 with up to two years of follow up. (2) Methods: A total of 56 patients with CIN 1, ten with CIN 2, and 14 patients for the placebo group were enrolled in this study. (3) Results: 75% (n = 42) of CIN 1 patients presented a complete response to PDT and only 23.2% (n = 13) of recurrence, progression, and/or lesions remaining two years after PDT. For CIN 2/3 patients, 90% were observed to be cured after one and two years of follow up. (4) Conclusions: PDT presented best results two years after a non-invasive, fast, and low-cost procedure and in comparison with the placebo group, preventing the progression of cervical intraepithelial neoplasia and preserving the cervix.

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Efficacy and safety of photodynamic therapy for cervical intraepithelial neoplasia and human papilloma virus infection

Abstract: PDT that targets CIN or cervical HPV infection improves the CRR, but slightly compromises safety. Further studies are necessary to identify the most effective and least toxic photosensitizer.

Cited by 59 publications

References 35 publications

Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

Photodynamic Therapy Using a New Folate Receptor-Targeted Photosensitizer on Peritoneal Ovarian Cancer Cells Induces the Release of Extracellular Vesicles with Immunoactivating Properties

Photosensitizer Activation Drives Apoptosis by Interorganellar Ca2+ Transfer and Superoxide Production in Bystander Cancer Cells

Long Term Effectiveness of Photodynamic Therapy for CIN Treatment

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