Serum periostin levels in fibrous dysplasia: Its usefulness as disease biomarker. An exploratory study

Objective: Fibrous dysplasia (FD) is a rare, non-hereditary bone disease caused by a somatic mutation of GNAS gene. Periostin (Postn) is a new marker, linked to bone repair processes. We aimed to assess Postn sensitivity as disease activity marker of FD.Methods: An exploratory case-control study was led, with 15 FD patients, paired by age and gender with healthy subjects (controls). Postn serum levels were gauged in FD patients and controls, also according to clinical manifestation. In the same assay, with serum samples stored at -80°C, Postn was measured by the ELISA method (Sigma Aldrich; St. Louis, USA), [coefficient of variation (%CV) intra-assay <10% and interassay<12%]. Statistical analysis: an R Core Team 2018 processor wasused (https://www.R-project.org). A nonparametric test (MannWhitney)was used to compared Postn serum levels between the groups. ROC curves were used to find optimal cut-off points andanalyze Postn sensitivity (predictive value).Results: 15 FD patients (polyostotic 40%, monostotic 33% and McCune-Albright syndrome 27%), with an average age (X±DS) of 44.3±10 y. In our FD patient cohort, no statistically significantdifferences were observed between Postn and control group (FD: 51.1±10 ng/ml vs. control: 44.2±15 ng/ml; p=0.15) nor by FD clinical form (polyostotic: 51.8±9.1 ng/ml vs. monostotic:49.6±13 ng/ml; p=0.66). Figure 1 shows the ROC curve obtained and optimal cut-off points.Conclusion: Postn serum levels did not show statistically significant differences compared to control group or by clinical manifestation, showing low sensitivity as disease activity markerof FD.Funding: UBACYT 2018 (#0113).Fil: Mastaglia, Silvina Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: González, Diana. Mautalen Salud e Investigación ; ArgentinaFil: Tetzlaff, T. W.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Fisiopatología y Bioquímica Clínica; ArgentinaFil: Bonanno, Marina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Gianotti, G. R.. Mautalen Salud e Investigación ; ArgentinaFil: Fernández, F. C.. Mautalen Salud e Investigación ; ArgentinaFil: Gómez Glorioso, G. G. D.. Mautalen Salud e Investigación ; ArgentinaFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaWorld Congress on Osteoporosis, Osteoarthritis and Musculoskeletal DiseasesBarcelonaEspañaInternational Osteoporosis FoundationEuropean Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Disease

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Role of Radiotherapy in Aggressive Digital Papillary Adenocarcinoma.

Aggressive digital papillary adenocarcinoma (ADPA) is a rare and often misdiagnosed malignant tumor of the sweat glands, most commonly encountered on the extremities. Due to the relatively high metastatic potential of the tumor, aggressive surgical treatment, including amputation, is generally recommended. We present a case of a 36-year-old male with an over 10-year history of a skin lesion on the right hand in the web space between the index and the middle finger. Histologically, the lesion revealed a malignant epithelioid neoplasm with features consistent with ADPA. The lesion was treated with 5-weeks preoperative radiation (total 5000 cGy) followed by surgical resection. There was no evidence of residual disease confirmed by pathological study of re-excision specimen as well as imaging studies. This is, to the best of knowledge, the first report of complete regression of an ADPA after radiotherapy

Pathological Features and Clinical Course in Patients With Recurrent or Malignant Orbital Solitary Fibrous Tumor/Hemangiopericytoma

A risk assessment score for metastasis based on age, tumor size, and mitotic figures has been suggested for nonorbital solitary fibrous tumor (SFT)/hemangiopericytoma. The authors herein examine the clinicopathological features of recurrent and metastatic orbital SFT and evaluate the existing risk assessment score for orbital SFT. The American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database was queried for patients with recurrent or malignant orbital hemangiopericytoma/SFT. The medical records were reviewed for clinical and pathologic findings, treatments, and outcomes. Eight patients from 3 institutions were identified with recurrent orbital hemangiopericytoma/SFT. Median age at diagnosis was 59 years, and 4 patients were women. The mean size of tumor was 2.1 ± 1.1 cm. All patients were initially treated with surgery and experienced local recurrence after a median of 4 (range 0.5-10) years. Five patients were treated with orbital radiation. Two patients also developed distant metastases and eventually died of their disease. Median Ki-67 was 5% (range 1-65%) and 5 mitotic figures/10 high-power fields (range 2-30). The previously described risk stratification model for nonorbital SFT did not correlate with the propensity to develop metastases in this cohort; however, both patients with distant metastasis had > 4 mitotic figures /10 high-power fields. In this cohort of recurrent orbital hemangiopericytoma/SFT, median time to recurrence was 4 years underscoring the importance of careful continued follow-up. The current risk stratification models have limited use for orbital lesions, mostly due to the fact that orbital SFTs are smaller than even the smallest size criteria in this risk assessment model

Teilprojektübergreifende Zusammenarbeit bei der Entwicklung von Anpassungsmaßnahmen der Landwirtschaft an sommerliche Trockenheit

Die projizierte Klimaänderung für die Metropolregion Hamburg (MRH) führt vermehrt zu sommerlichen Trockenperioden. Besonders im Südosten der Region wird dadurch die Wasserverfügbarkeit als limitierender Produktionsfaktor in der Landwirtschaft weiter begrenzt. Eine Abnahme der Grundwasserneubildung und zugleich zunehmender Wasserbedarf der Pflanzen erfordert eine Anpassung der Bewässerungsmethoden und Landbewirtschaftung. Dazu untersuchen Projekte innerhalb des KLIMZUG-NORD Themenfelds T3 „Zukunftsfähige Kulturlandschaften“ die Auswirkungen des Klimawandels auf die Verfügbarkeit und Qualität des Wassers und entwickeln entsprechende Anpassungsmaßnahmen der Landwirtschaft bei gleichzeitiger Berücksichtigung der Ansprüche des Naturschutzes. Es wurden Kooperationen zwischen Akteuren aus Forschung, Planung, Wasser- und Landwirtschaft gebildet und vertieft; im Folgenden sind Ausschnitte der interdisziplinären Zusammenarbeit in den Modellregionen Lüneburger Heide und Biosphärenreservat Niedersächsische Elbtalaue präsentiert