Ldrb toxin with in vitro and in vivo antitumor activity as a potential tool for cancer gene therapy

Due to the high prevalence of cancer in recent years, it is necessary to develop new and more effective therapies that produce fewer side effects. Development of gene therapy for cancer based on the use of suicide genes that can damage the tumor cell, without requiring a prodrug for its lethal effect, is one of the recent foci of gene therapy strategies. We evaluated the cytotoxic impact of the LdrB toxin from Escherichia coli k12 as a possible tool for cancer gene therapy. For that, colorectal and breast cancer cells were transfected under the control of a TRE3G promoter inducible by doxycycline. Our results showed that ldrB gene expression induced a drastic inhibition of proliferation in vitro, in both 2D and 3D experimental models. Moreover, unlike conventional chemotherapy, the ldrB gene induced a severe loss of proliferation in vivo without any side effects in our animal model. This antitumor outcome was modulated by cell cycle arrest in the G0/G1 phase and apoptotic death. Scanning electronic microscopy demonstrates that the LdrB toxin conserves its pore-forming ability in HCT-116 cells as in E. coli k12. Taken together, our results provide, for the first time, a proof of concept of the antitumor capacity of the ldrB gene in colorectal and breast cancer.This research was supported by the Fundación Mutua Madrileña (project FMM-AP16683-2017), Consejería de Salud Junta de Andalucía (PI-0089-2017), the MNat Scientitc Unit of Excellence (UCE.PP2017.0f), and from the Chair “Doctors Galera-Requena in cancer stem cell research”

Salivary Markers of Oxidative Stress in Patients Undergoing Orthodontic Treatment with Clear Aligners versus Self-Ligating Brackets: A Non-Randomized Clinical Trial

The aim of this work was to determine advanced the oxidative protein products (AOPPs), total antioxidant capacity (TAC), and myeloperoxidase activity (MPO) in the saliva of patients undergoing orthodontic treatment with clear removable aligners in comparison with another group in treatment with fixed passive self-ligating brackets applying light forces, before treatment, after 30 days, and after 90 days of treatment. This non-randomized clinical trial recruited patients consecutively, all of which were over 18 years of age and due to undergo orthodontic treatment. They were divided into two groups according to treatment type: Group A, 48 patients treated with clear aligners (Invisalign®); and Group B, 19 patients treated with Damon System® 0.22” self-ligating brackets applying light forces. Saliva samples were collected by a single clinician following the same protocol and underwent three analyses—AOPPs, TAC, and MPO levels–at baseline before placing the apparatus, after 30 days, and after 90 days treatment. Orthodontic treatment, whether with clear aligners or fixed self-ligating brackets and light forces, increased AOPPs after the first 30 days of treatment. During the initial phases of orthodontic treatment, neither clear aligners nor fixed self-ligating brackets applying light forces showed changes in TAC and MPO. Orthodontic treatment with both clear aligners and fixed apparatus self-ligating brackets applying light forces increases oxidative stress (AOPPs) after the first 30 days of treatment. There are no differences in AOPP levels between treatment with clear aligners and self-ligating brackets during the first 90 days of treatment. The antioxidative capacity of saliva during the initial phases of orthodontic treatment, whether with self-ligating brackets or clear aligners, does not undergo significant changes. With either orthodontic technique, the patients’ salivary antioxidant capacity is similar