Introduction Homologous recombination repair (HRR) is a critical pathway for the repair of DNA damage caused by cisplatin or PARP inhibitors. HRR may be impaired by multiple mechanisms in cancer, which complicates assessing the functional HRR status in cells. Here, we monitored the ability of non-small cell lung cancer (NSCLC) cells to form subnuclear foci of DNA repair proteins as a surrogate of HRR proficiency. Methods We assessed clonogenic survival of 16 NSCLC cell lines in response to cisplatin, mitomycin C (MMC), and the PARP inhibitor olaparib. Thirteen tumor explants from NSCLC patients were subjected to cisplatin ex-vivo. Cells were assayed for foci of repair-associated proteins such as BRCA1, FANCD2, RAD51, and γ-H2AX. Results Four cell lines (25%) showed an impaired RAD51 foci forming ability in response to cisplatin. Impaired foci formation correlated with cellular sensitivity to cisplatin and MMC as well as olaparib. Foci responses complemented or superseded genomic information suggesting alterations in the ATM/ATR and FA/BRCA pathways. Because baseline foci in untreated cells did not predict drug sensitivity we adapted an ex-vivo biomarker assay to monitor damage-induced RAD51 foci in NSCLC explants from patients. Ex-vivo cisplatin treatment of explants identified 2 tumors (15%) exhibiting compromised RAD51 foci induction. Conclusions A fraction of NSCLC harbors HRR defects that may sensitize the affected tumors to DNA damaging agents including PARP inhibitors. We propose that foci-based functional biomarker assays represent a powerful tool for prospective determination of treatment sensitivity, but will require ex-vivo techniques for induction of DNA damage to unmask the underlying HRR defect.
Introduction. Face transplantation (FT) is an innovative achievement of modern reconstructive surgery and is on the verge of becoming a common surgical opportunity. This review article was compiled to provide an update on this surgical field, especially regarding clinical outcomes, benefits, and complications implied. Methods. We performed an extensive research on all English-language Medline articles, case reports, and reviews published online until September 15, 2013. Used search terms were “face transplantation,” “face transplant,” “facial transplantation,” “facial transplant,” “face allograft,” and “facial allograft.” Results. To date 27 FTs have been performed worldwide. 19 of these cases have been published in the Medline database. Long-term follow-up reports of FT cases are rare. Three deaths associated with the procedure have occurred to date. The clinical outcomes of FT are satisfying. Reinnervation of sensation has been faster than motor recovery. Extensive functional improvements have been observed. Due to strict immunosuppression protocols, no case of hyperacute or chronic rejection and no graft-versus-host disease have occurred to date. Conclusions. As studies on long-term outcomes are missing, particularly regarding immunosuppression-related complications, FT will stay experimental for the next years. Nevertheless, for a small group of patients, FT already is a feasible reconstructive option.
Temporomandibular joint osteoarthritis (TMJ-OA) is a chronic degenerative disease that is often characterized by progressive impairment of the temporomandibular functional unit. The aim of this randomized controlled animal trial was a comparative analysis regarding the chondroregenerative potency of intra-articular stem/stromal cell therapy. Four weeks after combined mechanical and biochemical osteoarthritis induction in 28 rabbits, therapy was initiated by a single intra-articular injection, randomized into the following groups: Group 1: AB Serum (ABS); Group 2: Hyaluronic acid (HA); Group 3: Mesenchymal stromal cells (STx.); Group 4: Mesenchymal stromal cells in hyaluronic acid (HA + STx.). After another 4 weeks, the animals were euthanized, followed by histological examination of the removed joints. The histological analysis showed a significant increase in cartilage thickness in the stromal cell treated groups (HA + STx. vs. ABS, p = 0.028; HA + ST.x vs. HA, p = 0.042; STx. vs. ABS, p = 0.036). Scanning electron microscopy detected a similar heterogeneity of mineralization and tissue porosity in the subchondral zone in all groups. The single intra-articular injection of a stem cell containing, GMP-compliant advanced therapy medicinal product for the treatment of iatrogen induced osteoarthritis of the temporomandibular joint shows a chondroregenerative effect.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.