Isocitrate dehydrogenase 1 (IDH1) decarboxylates isocitrate to α-ketoglutarate (α-KG) leading to generation of NADPH, which is required to regenerate reduced glutathione (GSH), the major cellular ROS scavenger. Mutation of R132 of IDH1 abrogates generation of α-KG and leads to conversion of α-KG to 2-hydroxyglutarate. We hypothesized that glioma cells expressing mutant IDH1 have a diminished antioxidative capacity and therefore may encounter an ensuing loss of cytoprotection under conditions of oxidative stress. Our study was performed with LN229 cells stably overexpressing IDH1 R132H and wild type IDH1 or with a lentiviral IDH1 knockdown. Quantification of GSH under basal conditions and following treatment with the glutathione reductase inhibitor BCNU revealed significantly lower GSH levels in IDH1 R132H expressing cells and IDH1 KD cells compared to their respective controls. FACS analysis of cell death and ROS production also demonstrated an increased sensitivity of IDH1-R132H-expressing cells and IDH1 KD cells to BCNU, but not to temozolomide. The sensitivity of IDH1-R132H-expressing cells and IDH1 KD cells to ROS induction and cell death was further enhanced with the transaminase inhibitor aminooxyacetic acid and under glutamine free conditions, indicating that these cells were more addicted to glutaminolysis. Increased sensitivity to BCNU-induced ROS production and cell death was confirmed in HEK293 cells inducibly expressing the IDH1 mutants R132H, R132C and R132L. Based on these findings we propose that in addition to its established pro-tumorigenic effects, mutant IDH1 may also limit the resistance of gliomas to specific death stimuli, therefore opening new perspectives for therapy.

Introduction Autologous fat grafting (AFG) has both aesthetic and reconstructive applications. Described by Neuber in 1893 there are numerous applications of AFG as the body of evidence for its use has expanded. The earliest controversies were evident in lipofilling for breast defects post-oncological treatment, and to this day some countries do not allow it for fear of inducing tumourogenesis in an oncologically ablated field. Adipose-derived stem cells (ASCs) have been shown pro-oncologic behaviour in xenografts, however, this has not been reproduced in clinical observations thus far. Material and Methods We sought to review contemporary harvesting and processing techniques for AFG in the craniofacial region, therefore distributed a survey to evaluate the opinion and clinical impact of oncological risk across four European countries with possibly differing clinical attitudes. Results In the craniofacial region AFG is mostly used for aesthetic indications, cannula hand-held aspiration and centrifugation seem to be the predominant harvesting and processing techniques. Half of our respondents tell patients about the possibility of pro-oncologic behaviour of AFG. We found no significant geographical differences between the German-speaking and the English groups concerning their harvesting and processing technique. German participants seem to perform AFG more often and mostly use it for cosmetic and post-cancer treatment sequelae, English participants homogenically use AFG for cosmetic reasons. Conclusion Theoretical pro-oncologic behaviour of craniofacial AFG does not deter surgeons. Perhaps, we shouldn’t consider discussing this complex area of oncogenesis with patients as there is no elevated risk from what we know.

Background: Autologous fat grafting (AFG) is evolving in both aesthetic and reconstructive applications, since the body of evidence for its use has expanded. The earliest controversies were evident in lipofilling for oncological breast reconstruction, and to this day, some countries do not allow it for fear of inducing tumourigenesis in an oncologically ablated field. Methods:We sought to review contemporary harvesting and processing techniques for AFG in the craniofacial region, therefore distributed a survey to evaluate the clinical impact of oncological risk across four European countries.Results: We found no significant geographical differences between the German-speaking and the English groups concerning their harvesting and processing technique. Half of our respondents discuss the possibility of pro-oncologic behavior of AFG. Conclusion:AFG harvesting and processing techniques do not considerably vary by geography. Further studies should evaluate oncologic risk potential of AFG in head and neck tumor sites, especially because there is no excellent article regarding this phenomenon.

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