Colorectal cancer is a worldwide health burden, with high incidence and mortality, especially in the advanced stages of the disease. Preclinical models are very important and valuable to discover and validate early and specific biomarkers as well as new therapeutic targets. In order to accomplish that, the animal models must replicate the clinical evolution of the disease in all of its phases. In this article, we review the existent mouse models, with their strengths and weaknesses in the replication of human cancer disease progression, with major focus on orthotopic models. K E Y W O R D Scolorectal cancer, mouse model, orthotopic model

This study investigated the microleakage of two different root canal obturation systems, using the nuclear medicine approach, with sodium pertechnetate 99m Tc. Twenty six single-rooted extracted teeth were selected. The crowns were sectioned to obtain 15 mm long root segments and each tooth was prepared using rotary ProFile ® instruments. The roots were divided into 2 experimental groups and two control groups. Twenty root canals were filled, using Thermafil ® and Topseal ® or MTA Fillapex ® as a sealer. On the 7th and the 28th day the apices were submersed in a solution of 99m Tc-Pertechnetate during 3 hours. The radioactivity was counted using a gamma camera. Although apical leakage on the 7th day in the Topseal group was reduced compared with RealSeal1, with a statistical significant difference (p = 0.057), on the 28th day, the MTA Fillapex increased the sealing properties (p = 0.017).

PURPOSE:To investigate the impact of selective hepatic artery clamping (SHAC) in hepatocellular function. METHODS:Three groups of Wistar male rats were subjected to SHAC ischemia period of 60min: Group A continuous SHAC were subjected to SHAC ischemia period of 60min, Group B intermittent SHAC of 30min with 5min of reperfusion and Group C intermittent SHAC of 15min with 5min of reperfusion. Animals without SHAC were included-Group D. To evaluate hepatocellular function blood markers and hepatic extraction function (HEF) using 99m Tc-mebrofenin were performed before and after surgery. Flow cytometry was used to analyze oxidative stress and cell viability. RESULTS:A mortality rate of 7.6% in Group A was observed. HEF maintained normal values between the groups. Flow cytometry demonstrated no significant differences between the groups in viability, type of cell death as well as in the production of reactive oxygen species. CONCLUSIONS: The selective hepatic artery clamping compared to other clamping techniques results on increased cell viability and decreased hepatocyte death. The SHAC is a potential alternative to decrease per-operative bleeding while maintaining hepatocellular function.

Perinatal derivatives (PnD) are gaining interest as a source for cell-based therapies. Since the eye is easily accessible to local administration, eye diseases may be excellent candidates to evaluate novel therapeutic approaches. With this work, we performed a systematic review of published preclinical and clinical studies addressing PnD in the treatment of ocular diseases. We have set two specific objectives: (i) to investigate the current level of standardization in applied technical procedures in preclinical studies and (ii) to assess clinical efficacy in clinical trials. Hereto, we selected studies that applied amniotic membrane (hAM) and mesenchymal stromal cells derived from amniotic membrane (hAMSC), placenta (hPMSC), umbilical cord (hUC-MSC) and Wharton’s Jelly (hUC-WJ-MSC), excluding those where cells were not transplanted individually, following a systematic PubMed search for preclinical studies and consultation of clinical studies on https://clinicaltrials.gov and https://www.clinicaltrialsregister.eu/. Our bibliographic search retrieved 26 pre-clinical studies and 27 clinical trials. There was a considerable overlap regarding targeted ocular structures. Another common feature is the marked tendency towards (i) locally administered treatments and (ii) the PnD type. In the cornea/ocular surface, hAM was preferred and usually applied directly covering the ocular surface. For neuroretinal disorders, intra-ocular injection of umbilical or placental-derived cells was preferred. In general, basic research reported favourable outcomes. However, due to lack of standardization between different studies, until now there is no clear consensus regarding the fate of administered PnD or their mode of action. This might be accountable for the low index of clinical translation. Regarding clinical trials, only a minority provided results and a considerable proportion is in “unknown status”. Nevertheless, from the limited clinical evidence available, hAM proved beneficial in the symptomatic relief of bullous keratopathy, treating dry eye disease and preventing glaucoma drainage device tube exposure. Regarding neuroretinal diseases, application of Wharton’s Jelly MSC seems to become a promising future approach. In conclusion, PnD-based therapies seem to be beneficial in the treatment of several ocular diseases. However, much is yet to be done both in the pre-clinical and in the clinical setting before they can be included in the daily ophthalmic practice.