# Photodynamic Therapy Effects on Oral Dysplastic Keratinocyte Cell Cultures: A Systematic Review
## 3 Results  
The preliminary search resulted in 75 studies, out of which 22 were found to be duplicates. After reviewing the titles and abstracts of the remaining 53 studies, 45 were rejected as they did not meet the inclusion criteria (English article; in vitro studies; not review articles; published since 1990). Further evaluation of the full texts led to the exclusion of only one article, since the full text was not available. As a result, seven studies were ultimately identified and included in the analysis. The information regarding these seven selected articles, including details such as the type of photosensitizer, the light source used, the cell lines, and the methodology, are summarized in Table 1. The risk of bias of the studies was assessed with QUIN Tool. Three studies were evaluated as medium-risk (<70% QUIN Tool score), four as low-risk (>70% QUIN Tool score), and noon as serious-risk (<50% QUIN Tool score). The extrapolated data had some heterogeneity that did not allow for a meta-analysis. All the studies provide sound evidence, and none presented a critical RoB in any domain (Table 2). The paper from [PERSON] et al. [24] investigated the effectiveness of erythrosine as a photosensitizer for Photodynamic Therapy of oral malignancies. The study found that erythrosine was taken up by both malignant and pre-malignant oral epithelial cells in a dose-dependent manner. However, the percentage of cell killing observed following PDT differed between the two cell lines, with a maximum of 80% for pre-malignant cell killing achieved compared to 60% killing for malignant cells. The study also found that both cell types exhibited predominantly mitochondrial accumulation of erythrosine, but the mitochondrial transmembrane potential (DYm) studies showed that the malignant cells were far more resistant to the changes in DYm when compared to the pre-malignant cells. Finally, cell death morphology and caspase activity analysis \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline \multirow{2}{*}{**Study**} & \multirow{2}{*}{**Population**} & \multirow{2}{*}{**Intervention (Light Source)**} & \multirow{2}{*}{**Intervention (PS)**} & \multirow{2}{*}{**Comparison**} & \multirow{2}{*}{**Methodology**} & \multirow{2}{*}{**Outcome**} \\ \hline \multirow{8}{*}{[PERSON] et al. (2020) [29]} & \multirow{8}{*}{DOK} & He–Ne ion laser & & Groups were & \multirow{8}{*}{PDT effect was assessed with} & ALA-PDT for killing oral \\  & & He–Ne ion laser & & different doses of & & \\  & (635 nm; & & & & \\  & 18 mW/cm\({}^{2}\); & 10 & Acid (ALA) & 1, or 2 mM), & & \\  & & J/cm\({}^{2}\)) & & comparison was & & \\  & & & & CAL-27 (OSCC cell lines) & & \\ \hline \multirow{8}{*}{[PERSON] et al. (2022) [30]} & \multirow{8}{*}{DOK} & He–Ne ion laser & & Groups were & \multirow{8}{*}{ADA patch for the in vitro (635 nm; 108 / cm\({}^{2}\)), 200 mW/cm\({}^{2}\)} & & \\  & & & & subdivided by & & \\  & & & application of & & \\  & & & AL-PDT and & & & \\  & & & AALA-PADT and & & & \\  & & & AALA-PADT, & & & \\  & & & AALA-PADT, & & & \\  & & & AALA-PADT, & & & \\  & & & AALA-PADT, & & & \\  & & & AALA patch for the in vitro (635 nm; 108 / cm\({}^{2}\); & & \\  & & & dry hydrogel patch & & \\  & & & (PACA) & & \\  & & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Cont. studies demonstrated the occurrence of extensive necrosis with high-dose PDT in pre-malignant cells, whereas apoptosis was observed at lower doses of PDT for both cell lines. [PERSON] et al., in 2014 [27], explored the molecular mechanisms activated by PDT using aluminum disulfonated phthalocyanine in dysplastic human oral keratinocytes. The study found that PDT leads to the induction of apoptosis in tumoral cells via the intrinsic mitochondrial apoptotic pathway. The protein microarray analysis was used to evaluate the possible molecular pathways by which PDT activates apoptosis in dysplastic oral keratinocytes cells.