This could be CH5424802 of interest in situations of repeated chemotherapy administration schemes for clinical translation in patients. In this study, we chose to only study the short-term effect of L-PDT on IFP and TBF as chemotherapy was administered once, and its distribution was assessed after 1 hour. It is mandatory to further determine how L-PDT affects

the tumor and normal vasculatures for longer periods of time and how this affects subsequent administrations of chemotherapy. In addition, these observations further underline the need to obtain specific biomarkers for L-PDT assessment in patients to better optimize treatments. A clinical translation of our study in patients, although the procedure remains complex and invasive, could be of interest in superficially spreading tumors such as mesotheliomas or oligometastatic pleural disseminations. Indeed, this therapy has limited side effects and an important effect on drug distribution enhancement. However, optimal drug/light conditions

are mandatory for tumor blood vessel L-PDT to be successful. GW 572016 Therefore, a better understanding of how photosensitization modifies the vascular function and refinements of in situ L-PDT monitoring are mandatory for the translation of this concept in a clinical setting. Few parameters currently exist to assess the impact of L-PDT on the vasculature and thus determine the appropriate sequence of administration of chemotherapy following L-PDT for best therapeutic results. On the basis of our study, we find two promising factors, IFP and TBF, that could be translated in the clinics after validation to monitor

the effect of L-PDT on solid tumors. The application of L-PDT in combination with chemotherapy could thus be performed using the wick-in-needle technique in vivo with laser Doppler flowmetry to monitor and confirm the vascular effect of L-PDT. Therefore, IFP and TBF could represent two potential biomarkers that could be used for L-PDT translation in the clinics. Other biomarkers such as circulation angiogenic factors over time and imaging of vessel permeability by Magnetic PLEK2 Resonnance Imaging (MRI), for example, should also be exploited. These elements have shown robustness in clinical trials combining antiangiogenic therapy with chemotherapy in the aim to optimize the normalization concept. In the L-PDT field, no studies have so far been performed with this concept. These elements therefore require validation but could be of interest to translate L-PDT in the clinics. In conclusion, Visudyne-mediated L-PDT has the potential to selectively enhance Liporubicin distribution in tumors in a model of sarcoma metastasis to the lung by reducing tumor IFP. The enhancement of convection in tumors by L-PDT is a novel and attractive concept that opens new perspectives for the management of superficially spreading tumors. We are grateful to N.