BackgroundChronic periodontal disease is an infectious disease consisting of prolonged inflammation of the supporting tooth tissue and resulting in bone loss. Guided bone regeneration procedures have become common and safe treatments in dentistry, and in this context dental stem cells would represent the ideal solution as autologous cells. In this study, we verified the ability of dental pulp mesenchymal stem cells (DPSCs) and gingival mesenchymal stem cells (GMSCs) harvested from periodontally affected teeth to produce new mineralized bone tissue in vitro, and compared this to cells from healthy teeth.MethodsTo characterize DPSCs and GMSCs, we assessed colony-forming assay, immunophenotyping, mesenchymal/stem cell phenotyping, stem gene profiling by means of flow cytometry, and quantitative polymerase chain reaction (qPCR). The effects of proinflammatory cytokines on mesenchymal stem cell (MSC) proliferation and differentiation potential were investigated. We also observed participation of several heat shock proteins (HSPs) and actin-depolymerizing factors (ADFs) during osteogenic differentiation.ResultsDPSCs and GMSCs were successfully isolated both from periodontally affected dental tissue and controls. Periodontally affected dental MSCs proliferated faster, and the inflamed environment did not affect MSC marker expressions. The calcium deposition was higher in periodontally affected MSCs than in the control group.Proinflammatory cytokines activate a cytoskeleton remodeling, interacting with HSPs including HSP90 and HSPA9, thioredoxin-1, and ADFs such as as profilin-1, cofilin-1, and vinculin that probably mediate the increased acquisition in the inflamed environment.ConclusionsOur findings provide evidence that periodontally affected dental tissue (both pulp and gingiva) can be used as a source of MSCs with intact stem cell properties. Moreover, we demonstrated that the osteogenic capability of DPSCs and GMSCs in the test group was not only preserved but increased by the overexpression of several proinflammatory cytokine-dependent chaperones and stress response proteins.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0633-z) contains supplementary material, which is available to authorized users.

Background: Despite the survival advantage, not all metastatic renal cell carcinoma (mRCC) patients achieve a long-term benefit from immunotherapy. Moreover, the identification of prognostic biomarkers is still an unmet clinical need. Methods: This multicenter retrospective study investigated the prognostic role of peripheral-blood inflammatory indices and clinical factors to develop a novel prognostic score in mRCC patients receiving at least second-line nivolumab. The complete blood count before the first cycle of therapy was assessed by calculating neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), and systemic inflammation response index (SIRI). Clinical factors included pre-treatment International Metastatic RCC Database Consortium (IMDC) score, line of therapy, and metastatic sites. Results: From October 2015 to November 2019, 571 mRCC patients received nivolumab as second- and further-line treatment in 69% and 31% of cases. In univariable and multivariable analyses all inflammatory indices, IMDC score, and bone metastases significantly correlated with overall survival (OS). The multivariable model with NLR, IMDC score, and bone metastases had the highest c-index (0.697) and was chosen for the developing of the score (Schneeweiss scoring system). After internal validation (bootstrap re-sampling), the final index (Meet-URO score) composed by NLR, IMDC score, and bone metastases had a c-index of 0.691. It identified five categories with distinctive OSs: group 1 (median OS – mOS = not reached), group 2 (mOS = 43.9 months), group 3 (mOS = 22.4 months), group 4 (mOS = 10.3 months), and group 5 (mOS = 3.2 months). Moreover, the Meet-URO score allowed for a fine risk-stratification across all three IMDC groups. Conclusion: The Meet-URO score allowed for the accurate stratification of pretreated mRCC patients receiving nivolumab and is easily applicable for clinical practice at no additional cost. Future steps include its external validation, the assessment of its predictivity, and its application to first-line combinations.

Our objective was to evaluate the biodistribution, kinetics, and radiation dosimetry of CuCl in humans and to assess the ability of CuCl PET/CT to detect prostate cancer (PCa) recurrence in patients with biochemical relapse. We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external-beam radiation therapy. All patients underwentCuCl PET/CT, F-choline PET/CT, and multiparametric MRI within 15 d of each other. Experienced readers interpreted the images, and the detection rate (DR) of each imaging modality was calculated. Histopathology, when available; clinical or laboratory response; and multidisciplinary follow-up were used to confirm the site of disease. In parallel, biodistribution, kinetics of the lesions, and radiation dosimetry ofCuCl were evaluated. From a dosimetric point of view, an administered dose of 200 MBq forCuCl translated into a 5.7-mSv effective dose. Unlike F-choline,CuCl was not excreted or accumulated in the urinary tract, thus allowing thorough pelvic exploration. The maximum CuCl uptake at the sites of PCa relapse was observed 1 h after tracer injection. In our cohort, CuCl PET/CT proved positive in 41 of 50 patients, with an overall DR of 82%. The DRs of F-choline PET/CT and multiparametric MRI were 56% and 74%, respectively. The difference between the DRs ofCuCl PET/CT and F-choline PET/CT was statistically significant ( < 0.001). Interestingly, on considering prostate-specific antigen (PSA) value, CuCl PET/CT had a higher DR than F-choline PET/CT in patients with a PSA of less than 1 ng/mL. The biodistribution of CuCl is more suitable than that of F-choline for exploring the pelvis and prostatic bed. TheCuCl effective dose is like those of other established PET tracers. In patients with biochemical relapse and a low PSA level, CuCl PET/CT shows a significantly higher DR than F-choline PET/CT.

GX301 demonstrated to be safe and highly immunogenic. Further studies are needed to determine its clinical efficacy.