Effect of Shape on the Magnitude of the Delboeuf Illusion

Three experiments to discuss the applicability of the contour attraction and the parallel attraction to different shapes in the Delboeuf illusion. The contour attraction suggests that the contours of the test figure and the inducer have an effect of interattraction in the Delboeuf illusion, and the parallel attraction suggests that the attraction between non-intersecting contours was maximal when they were parallel. In Experiment 1, the shape of the test figures and the inducers changed simultaneously and formed parallel lines. In Experiment 2, the test figures remained circles while the inducers changed shape. Experiment 3 was identical to Experiment 2 except that the areas of the inducers remained equal. The results demonstrated that the illusion is influenced by shape. Importantly, the effect of shape on the magnitude of the Delboeuf illusion is based on the contour attraction and the parallel attraction. Configurations with circles or shapes more similar to a circle were related more to the contour attraction, whereas shapes that were dissimilar to a circle were related more to the parallel attraction. We suggest that the contour attraction may be a circular modality of the parallel attraction.

Rejuvenation of Stored Red Blood Cells Increases Oxygen Release Capacity

Introduction: The goal of a red blood cell (RBC) transfusion is to treat anemia and improve oxygen delivery to tissues (Sharma 2011). RBC metabolic changes during liquid storage increases the affinity of hemoglobin for oxygen by depletion of 2,3-diphosphoglycerate (2,3-DPG). This change reduces the partial pressure of O2 where the oxygen tension of hemoglobin is 50% saturated (p50). Transfusion of stored RBCs manifests immediate deficits in patient 2,3-DPG concentration after surgery with incomplete in vivo restoration 72 hours post-surgery (Scott 2016). This change may bring into question the efficiency of peripheral oxygen unloading of liquid stored RBCs following transfusion. Ex-vivo rejuvenation of allogeneic RBCs increases the levels of ATP and 2,3-DPG and increases the p50 of stored RBCs by right-shifting the Oxyhemoglobin Dissociation Curve (ODC) (Dennis 1979). RBC Oxygen Release Capacity (ORC) is determined by the percent of oxygen removed from hemoglobin across the arterial (100 mmHg O2) - venous (40 mmHg O2) pressure gradient (Li 2016). The objective was to evaluate the changes in 2,3-DPG and p50 during routine blood bank storage for 35 days and the impact on ORC after RBC rejuvenation. Methods: Five (5) units of human whole blood were collected in CPD, processed into leukocyte reduced RBC units and stored in an additive solution (AS-1). Nearly fresh RBC were obtained from a local blood center after days 3 - 6 of storage at 1-6 °C and then stored up to 35 days at 1-6 °C. A ten (10) mL aliquot was withdrawn from each unit on the day of receipt, then on Days 7, 14, 21, 28, and 35. Each aliquot was split equally by volume into Control (untreated) and Rejuvenated Groups (n=5 per group). The Rejuvenated samples (5 mL) were incubated with 0.8 mL rejuvesol™ Solution (Zimmer Biomet) in a dry air blood warmer (Sarstedt SAHARA-III) for one hour at 37 °C. Complete blood counts (CELL-DYN 3700), ODC (TCS Scientific Corp Hemox-Analyzer), and 2,3-DPG (Roche) on perchloric acid extracts were collected. The ORC was calculated from the ODC as previously described (Li 2016). Results: Five (5) units of CPD/AS-1 RBC units were received less than one week post-donation (5.0 ± 1.2 Days). As expected in the Control Group aliquots (n = 5), 2,3-DPG concentration and the p50 value declined significantly (p < 0.001, ANOVA) from Day 7 through Day 35 (Figure 1). Rejuvenated Group aliquots exhibited a significant increase in 2,3-DPG concentration and improved p50 (p < 0.001, t-test) at each storage interval after incubation with rejuvesol Solution compared to untreated Control aliquots (Figure 1). RBC rejuvenation shifted the ODC to the right (Figure 2) and significantly increased the ORC compared to Control aliquots (Figure 3). The ORC of Rejuvenated aliquots did not decline significantly with storage duration (p = 0.11, ANOVA) while Control aliquots were significantly impacted with storage duration (p < 0.001, ANOVA). Conclusion: Reduction in ORC with storage duration of unrejuvenated RBCs suggests impaired oxygen tissue delivery occurs with stored RBCs to the tissue microenvironment. Transfusion practices designed to increase hemoglobin concentration may be less effective with increased RBC age because of reduced oxygen release capacity. These in vitro results confirm previous reports regarding 2,3-DPG changes during storage and treatment with rejuvenation (Valeri 2000). Additional research is proposed to confirm these observations on full RBC units, the clinical impact of reduced oxygen release capacity, and what impact RBCs with a superphysiological ORC have on the tissue microenvironment. Figure 1 RBC p50 (mm Hg) and 2,3-DPG concentration (mmol/g Hb) for paired Rejuvenated and Control groups after storage for 3-6, 7, 14, 21, 28, and 35 days. 2,3-DPG and p50 values were significantly different between groups at each time-point (p < 0.001, t-test). Figure 1. RBC p50 (mm Hg) and 2,3-DPG concentration (mmol/g Hb) for paired Rejuvenated and Control groups after storage for 3-6, 7, 14, 21, 28, and 35 days. 2,3-DPG and p50 values were significantly different between groups at each time-point (p < 0.001, t-test). Figure 2 A representative ODC for a RBC aliquot stored for 21 days (Gray) and the "right-shift" of the curve with rejuvenation (Black) used to determine the ORC. The two vertical dashed lines represent the venous PO2 (40 mmHg) and arterial PO2 (100 mmHg). The solid line represents a typical p50 value of Control and Rejuvenated aliquots. Figure 2. A representative ODC for a RBC aliquot stored for 21 days (Gray) and the "right-shift" of the curve with rejuvenation (Black) used to determine the ORC. The two vertical dashed lines represent the venous PO2 (40 mmHg) and arterial PO2 (100 mmHg). The solid line represents a typical p50 value of Control and Rejuvenated aliquots. Figure 3 RBC ORC for paired Rejuvenated and Control groups after storage for 3-6, 7, 14, 21, 28, and 35 days. ORC was significantly different between groups at each time-point (p < 0.05, t-test). Figure 3. RBC ORC for paired Rejuvenated and Control groups after storage for 3-6, 7, 14, 21, 28, and 35 days. ORC was significantly different between groups at each time-point (p < 0.05, t-test). Disclosures Inglut: Zimmer Biomet: Employment. Kausch:Zimmer Biomet: Employment. Gray:Zimmer Biomet: Employment. Landrigan:Zimmer Biomet: Employment.

Impact of Routine Surveillance Imaging on Outcomes in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Undergoing Autologous Hematopoietic Cell Transplantation (auto-HCT)

Background It is common for diffuse large B-cell lymphoma (DLBCL) patients following autologous hematopoietic transplant (auto-HCT) to undergo surveillance imaging to monitor for lymphoma progression/relapse. Although a standard at most centers, this practice is not evidence-based, has not been shown to improve survival, and may pose a risk to patients due to radiation exposure. We studied DLBCL patients who underwent auto-HCT at three transplant centers to define how many surveillance imaging studies were obtained, how often relapses were detected by surveillance imaging versus clinically (based on signs, symptoms or laboratory findings), and whether survival was improved if relapse was detected by imaging versus clinically. Methods DLBCL patients who underwent auto-HCT during 2000-2013 were identified using clinical databases. Pre-transplant patient and disease characteristics were collected. Progression-free survival (PFS) and overall survival (OS) were determined. Patients were classified as having "radiographic" or "clinical" relapses. PFS and OS were compared for these two groups. Results A total of 209 patients with DLBCL who underwent auto-HCT between 2000 and 2013 were identified. There was insufficient follow-up information on 15 patients and hence only 194 patients were evaluable. Of these, 22 patients relapsed or progressed prior to or at their initial post-transplant disease assessment (day 100 evaluation). The remaining 172 patients were then analyzed to determine which patients relapsed and how relapses were detected. 48 patients relapsed at a median time of 287 days post-transplant. Of these patients, 14 (29%) had relapse detected clinically and 34 (71%) had relapse detected by surveillance imaging. Comparing the radiographic and clinically detected groups, median PFS post auto-HCT was 218 vs 402 days respectively (p= 0.49, log rank test, Figure 1) and median survival post auto-HCT was 643 vs 615 days respectively (p= 0.44, log rank test, Figure 1). For patients who never relapsed after auto-HCT, a median of 4 surveillance imaging studies were performed (with median follow up of 3.0 years post-transplant). Conclusions In DLBCL patients post auto-HCT, the majority of relapses were detected by surveillance imaging. However, the survival of patients with relapse detected by surveillance imaging was not superior to those whose relapse was detected clinically. Given this, combined with the radiation exposure and cost associated with surveillance imaging, the practice of surveillance imaging post auto-HCT appears to have limited utility in DLBCL. Disclosures Hari: Janssen: Consultancy; Novartis: Consultancy; Spectrum: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Celgene: Consultancy; BMS: Consultancy. Hamadani:Takeda: Research Funding; Cellerant: Consultancy; Celgene: Consultancy; MedImmune: Consultancy. Fenske:Celgene: Honoraria; Pharmacyclics: Honoraria; Seattle Genetics: Honoraria; Millennium/Takeda: Research Funding.

Predicting Time to Treatment in Follicular Lymphoma Using Population-Based Data

Introduction Patients diagnosed with Follicular Lymphoma (FL) either require immediate immuno-chemotherapy or, may simply be observed until the development of symptoms suggests that treatment should be initiated. Although there is no evidence to indicate that early intervention in asymptomatic, stage II - IV disease improves outcomes, both doctors and patients find "watch and wait" (W+W) strategies difficult to accept as it leaves considerable uncertainty as to the future. The ability to predict the likely time to treatment (TTT) being required would be helpful, both to give reassurance in cases where the likelihood of therapy in the near future is low and to identify higher risk cases where close observation or early intervention might be justified. Prognostic indices are usually derived using data from clinical trials or institutional datasets where patients who do not require treatment tend to be underrepresented; accordingly we constructed an improved prognostic index for TTT for those patients initially on a W+W strategy in an unselected, population-based cohort. Methods This study was based on an established population-based cohort, which since 2004 has tracked all patients newly diagnosed with a haematological malignancy in a representative UK population of nearly 4 million people (www.hmrn.org). All diagnoses, including disease progressions and transformations, are made by a single specialist haematopathology laboratory (www.hmds.info), and clinical teams work to UK guidelines (www.bcshguidlines.com). Clinical and treatment information is systematically collected for all patients and survival data is acquired through links with national data sources. All 296 out of 741 patients newly diagnosed with FL from 2004-2011 initially managed by a W+W approach were included in the analyses and these patients were followed up to February 2015. Prognostic indices for TTT were constructed using the components of the Follicular Lymphoma International Prognostic Index (FLIPI) and other routinely measured clinical variables. Modern machine learning techniques were used, in particular the LASSO applied to semiparametric survival regression, using bootstrapped model selection to confirm Lasso variable selection. The appropriate functional forms for individual variables were chosen on the basis of the Akaike Information Criterion. Predictive performance was measured using area under the ROC curve (AUC) and the concordance index (C). Results With a median age of 65.4 years (range 21-95), 42% of patients were male, 16% had B-symptoms and 37% had stage IV disease at presentation. Median follow-up was 6.4 years; 83 patients were subsequently treated for FL, a further 34 patients transformed to diffuse large B-cell lymphoma and 9 others died from disease progression prior to receiving chemotherapy for FL; median time to these events was 1.4 years. Whilst the FLIPI score for patients initially managed on W+W was predictive for TTT (Figure 1) - achieving an AUC=0.64 and C=0.61, as a result of the model building process a proposed new index for TTT achieved AUC=0.75 and C=0.70 retaining blood albumin, haemoglobin, presence/absence of bulky disease (1/0 respectively) and a score based on the number of nodal sites in the prognostic model (Risk_Score = Albumin (g/dL) x 0.0412 + 0.719 * bulky_disease - 0.102 x Hb (g/dL) + 0.159 x nodal_score). The relation between index value and expected time-to-event for TTT is shown in Figure 2. Conclusion Our population-based data demonstrates that the FLIPI can be used to predict TTT in patients diagnosed with FL and put onto a W+W strategy. By utilising all of the information contained in the components of the FLIPI and by adding additional routine clinical factors we show that the accuracy of prediction of TTT can be improved leading to the production of an accurate and simple TTT curve that can be used in routine clinical practice. Figure 1. Time-to-treatment stratified by FLIPI (p = 0.0004 log-rank test) Figure 1. Time-to-treatment stratified by FLIPI (p = 0.0004 log-rank test) Figure 2. Expected Probability of Not Having Received Chemotherapy at 5 years After Diagnosis by Time-to-Treatment Risk Score Figure 2. Expected Probability of Not Having Received Chemotherapy at 5 years After Diagnosis by Time-to-Treatment Risk Score Disclosures Patmore: Gilead: Honoraria; Janssen: Honoraria.

Soluble LR11, GCSF−induced Migration Regulator from Myeloid Cells, Is Highly Increased in Chronic Myeloid Leukemia

Introduction: Chronic myeloid leukemia (CML) is characterized by the myeloproliferative clonal hyperplasia caused by the protein product of the BCR-ABL fusion gene. However, the mechanism underlying the release of increased numbers of myeloid cells from bone marrow (BM) to circulation which causes the accompanied remarkably high count of peripheral white blood cells (WBC) has not been fully elucidated. We have recently reported that G-CSF treatment induced the shedding of an LDL receptor family member LR11 (also called SorLA or SORL1) from myeloid cells, and the released soluble receptor accelerate the trans-endothelial migration of myeloid cells in cooperation with an endothelial activator, tumor necrosis factor-a (TNF-a) (Shimizu et al Ann Hematol 2014). Another group showed that the levels of TNF- a and G-CSF production by CML stem/progenitor cells were increased in the BM of CML. Thus, we hypothesized that the expanded mobilization of peripheral cells in CML is caused by the abnormally induced shedding activity which releases the two soluble key molecules for the migration of clonally expanded cells from BM to peripheral blood. Based on these backgrounds, we examined soluble LR11 levels in the BM of CML patients. Materials and methods: We analyzed 11 patients (comprising three CML, six acute myeloid leukemia (AML) and two immune thrombocytopenia (ITP)), who underwent bone marrow aspiration at the time of diagnosis in Chiba University Hospital between 2011 and 2012. We measured the levels of sLR11 in supernatants of BM by an ELISA method. We also examined the levels of TNF-a and MMP9 in some patients. Then we compared with clinical data including WBC and total nuclear cell count (TNC) of BM. Results: sLR11 levels of supernatant of BM in CML patients were significantly higher than AML patients (134.5+-215.7 ng/ml vs 15.0+-46.1 ng/ml, p=0.0389, Mann-Whitney test, Figure 1). The levels of two ITP patients were 14.8, 14.2 ng/ml respectively. There was no significant correlation between TNC and the levels of sLR11 (p=0.4386) in all patients. However, the WBC counts in CML patients (53,400+-60,253/ml) were slightly higher than AML patients (2970+-34,624/ml) (p=0.1967, Mann-Whitney test, Figure 2). We next evaluated myeloid TNF-a and MMP9 levels in patients with CML or other hematological malignancy). A CML patient revealed remarkably higher levels of TNF- a (16.8 pg/ml), and also MMP9 (22,000 pg/ml), compared with other hematological diseases. Conclusions: soluble LR11 levels were largely increased in the BM of patients with CML. Considering that the myeloid TNF-a level was increased in a case among them, the increased soluble LR11 in BM may induce myeloid cell release from BM into peripheral blood through the cooperative activation of trans-endothelial migration in cooperation with TNF-a. Figure 1. The levels of sLR11 in BM in patients with CML and AML. (p=0.0389) Figure 1. The levels of sLR11 in BM in patients with CML and AML. (p=0.0389) Figure 2. The WBC count in the patients, CML and AML. (p=0.1967) Figure 2. The WBC count in the patients, CML and AML. (p=0.1967) Disclosures No relevant conflicts of interest to declare.

Index to Predict MMR at 12 Months in Chronic Phase Chronic Myeloid Leukemia Patients Based on the Area Under the Lymphocyte Curve

BACKGROUND: Dasatinib is a second-generation BCR-ABL inhibitor that has a 325-fold higher potency than imatinib and a 16-fold higher potency than nilotinib in vitro. Recent reports suggested that absolute lymphocytosis in response to dasatinib for chronic phase (CP) –chronic myeloid leukemia (CML) might be associated with favorable response. However, as the fluctuation of lymphocytosis was often observed, it is sometimes difficult to define lymphocytosis. To evaluate how much increase and how long continuation of lymphocytosis affects the better clinical efficacy, we developed an index (DL index; Dasatinib induced Lymphocytosis index) that combines duration and increase of lymphocytosis. The aim of this study was to test the DL index as a predictor of Major Molecular Response (MMR) at 12 month. PATIENTS and METHODS: The DL area was based on a graph plotting the absolute lymphocyte counts and was the area under the lymphocyte curve using trapezoidal method. DL index was DL area divided by weeks. For example, DL index12W was defined as (DL area from 4 to 12 weeks) divided by (12-4) weeks. We tested the DL index12W in 30 patients who developed MMR at 12 months (MMR group) and 9 patients without MMR (non-MMR group). RESULTS and DISCUSSION: DL score12w in MMR group and non-MMR group were 2714.0 (95% CI; 2286.0-3142.2, n=30) and 1559.9 (95% CI; 1006.9- 2113.0, n=9) respectively. There was a significant difference between MMR group and non-MMR group in DL index12W by t-test(Figure 1, p=0.0016). A significant linear relationship was obtained between DL index12w and the peaked lymphocyte counts within 12 weeks by Spearman's correlation coefficient rank test (Figure 2, p=1.97E-07, correlation coefficient=0.91). The DL index12w, 2,113, which was the upper limit of non-MMR group 95% CI, is equivalent to 2,909/µl in lymphocyte count, and the DL index12w, 2,286, which is the lower limit of MMR group 95% CI, equivalent to 3,123/µl in lymphocyte count. Therefore, we divided all patients (n=39) into two groups, equal or more than 3,123/µl and less than 3,123/µl in the peaked lymphocyte counts. The patients with the peaked lymphocyte counts ≥ 3,123/µl reached MMR at 12 months (19/20=95.0%) to compare those less than 3,123/µl (11/19=57.9%) (p=0.0075). CONCLUSION: The peaked lymphocyte number, induced by the DL index12w, which calculation was extremely easy, was associated with molecular response. These data suggests that this tool can be useful in interpreting the results of molecular response at 12 months. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Cytogenetics As a Prognostic Factor Of The Overall Survival (OS) Of Mexican Patients With Myelodysplastic Syndrome (MDS)

Introduction MDS are a heterogeneous group of acquired clonal diseases, characterized by an increase of the apoptosis and several grades of cytopenias. They originate in hematopoietic stem cells with cytogenetic and molecular abnormalities, having the risk of evolving into an acute myeloid leukemia (AML). There are no clinical data of the characteristics of the patients with MDS in Mexico, thus we consider necessary to know the behavior of this disease in our population, also to evaluate the cytogenetic alterations, and to investigate whether they are associated with the OS. Methods A longitudinal-observational study was performed at the MDS clinic of the Hematology Department of the Specialties Hospital of the Centro Médico Nacional La Raza of the Instituto Mexicano del Seguro Social (IMSS), from January 25, 2005 to January 25, 2013. The primary objective was to evaluate the epidemiological characteristics and the cytogenetic findings of the patients with MDS in our population, establishing its correlation with the OS. We included patients >16 y.o., male and female, with diagnosis of newly diagnosed MDSs with a cytogenetic testing available (GGT-band analysis performed at Quest Diagnostics and Genetica Pre y Post Natal). SPSS version 20 was used for statistical analysis. Survival was evaluated through KM curve. A Multivariate analysis with logistic regression was performed in order to know the OR and 95% CI and a p<0.05 was accepted as statistically significant. Results A total of 92 patients were included, 44 (47.8%) men, and 48 (52.2%) women. The cytogenetic study was normal in 72 (78.3%) of the patients and 20% (21.7%) had an abnormal cytogenetic study. The cytogenetic abnormalities were as follows: 5 (25%) had complex karyotype, 3 (15%) had –Y, 2 (10%) hypodiploidy, 2 (10%) del9, 1 (5%) del7, 1 (5%) +9, 1 (5%) t 1;5, 1 (5%) 17p-, 1 (5%) del21, 1 (5%) +19, 1(5%) del5q y 1(5%) +8. 77 patients (83.7%) had favorable cytogenetic risk; 8 (8.7%) intermediate cytogenetic risk; and 7 (7.6%) poor risk. The IPSS risk stratification was: low risk in 33 (35.9%) of the patients, intermediate-1 risk in 39 (53.3%), intermediate 2 risk in 5 (5.4%), and high risk in 5 (5.4%). The median OS was 85 months (figure 1), with a median follow-up of 35 months (2-96 months). The median survival for the favorable cytogenetic risk was 82.7 months 95% CI; 74.7-90.6), for the intermediate cytogenetic risk 73.6 months (95% CI; 49.06-98.1), and for the poor cytogenetic risk, 46.8 months (95% CI; 10.6-18.4). The patients with favorable cytogenetic risk had a better survival than those with intermediate or poor cytogenetic risk (P= .001 Log-rank test). (Figure 2) Of the 92 patients, 10 (10.08%) progressed to acute myeloid leukemia the cytogenetic risk of these patients was as follows: 5 had a favorable risk karyotype and 5 had poor risk karyotype. The patients with favorable cytogenetic risk had a lower risk of progression in comparison with those with poor risk karyotype (P= 0.000). The median PFS to AML was 18.7 months (95 CI 4.1-33.2). Survival per cytogenetic risk group: for the favorable cytogenetic risk the median survival was 22.2 months 95% CI (.76-43), and for the poor cytogenetic risk it was 15.2 months, 95% CI (.0-36.8). (P= .362 Log-rank test). (Figure 3). The performance of the cytogenetic study to classify the patients and to estimate the IPSS is statistically associated with mortality (P 0.006). In the multivariate analysis was found that there is an association, independently of the cytogenetic study with favorable risk according to the IPSS, with the protection against mortality, with an OR=0.141, (95% CI 0.042-0.47). This confered a protection factor of 86% for the survival, independently of the treatment and the MDS type. Conclusion Cytogenetic alterations in MDS patients differs importantly from other reports, since only a 21.7% of our patients had an abnormal cytogenetic finding. Nevertheless cytogenetic evaluation was very important for this population since it confirmed its prognostic importance for the OS of the Mexican MDS patients. Disclosures: Nacho-Vargas: Novartis Oncologia Mexico: Employment. Romero-Salas:Novartis Oncologia Mexico: Employment.

Complement Component 3 (C3) Is Transcriptionally Regulated By TWIST1

C3, a central component of the complement system, is a plasma protein that is synthesized in the liver. We have found that malignant epithelial cells are also able to synthesize and secrete C3. The regulation of expression of the C3 gene in malignant cells is not well understood. We found that C3 is highly expressed in various cancer cell lines (Cancer Cell Line Encyclopedia: CCLE) and cancerous human patient tissues (The Cancer Genome Atlas: TCGA). We then explored which transcription factors were responsible for regulating C3 gene expression in ovarian cancer cells. To determine C3 transcription factors, we performed a gene promoter analysis, which identified a TWIST1-binding consensus motif on the C3 gene promoter. The TWIST proteins (TWIST1 and TWIST2) are well known transcription factors are associated with more advanced, invasive and metastatic lesions. There is significant evidence suggesting that TWIST1 promotes tumor progression. To investigate whether TWIST1 is a transcription factor of C3 in human ovarian cancer cells, we performed a chromatin immunoprecipitation (ChIP) analysis and confirmed TWIST1 binding at the C3 promoter (Figure 1A,1B and 1c). The C3 promoter binding affinity is 5.83-fold higher in Twist antibody used pull down compared to the IgG control (n=3, p=0.001, t-test, Figure 1C). To investigate the functional effect of TWIST1 binding to C3 promoter, we performed a Luciferase reporter gene analysis, showing that a mutant TWIST1 binding site on the C3 promoter decreases luciferase reporter gene activity (control vs. C3 vs. mC3=1 vs. 3.3 vs.1.8, n=3, p=0.01, t-test, Figure 1D and 1E). Figure 1 C3 is a target gene of TWIST1. Figure 1. C3 is a target gene of TWIST1. Next, we manipulated expression of the Twist1 gene in ovarian cancer cells and monitored its effect on C3 gene expression. Small interfering RNAs (siRNA) against Twist1 drastically reduced C3 expression (n=3, p=0.01, t-test, Figure 1F); on the other hand, transducing these cells with lentivirus containing Twist1 increased C3 expression (n=3, p=0.01, t-test, Figure 1G). Therefore, we conclude that there is a positive correlation between expression of C3 and TWIST1 in ovarian cancer cells. Taken together, these data provide evidence that a novel transcription factor of C3, TWIST1, upregulates C3 expression in malignant cancer cells, leading to an increase in cell proliferative potential. Disclosures: No relevant conflicts of interest to declare.

Cognitive Functions across the GNB3C825TPolymorphism in an Elderly Italian Population

To verify whether theC825Tpolymorphism of the GNB3 influences the response to neuropsychological tests, mini-mental state examination, digit span (DS), immediate and delayed prose memory, memory with interference at 10 and 30 seconds (MI 10 and 30), trail making tests (TMTs) A and B, abstraction task, verbal fluency (VF) test, figure drawing and copying, overlapping figures test and clock test were performed in 220 elderly men and women free from clinical dementia and from neurological and psychiatric diseases randomly taken from the Italian general population and analysed across theC825Tpolymorphism. The performance of DS, immediate and delayed prose memory, VF, and TMTs was worse in subjects who were TT for the polymorphism in comparison to the C-carriers. The performance of all tests declined with age. In the case of DS, immediate and delayed prose memory, MI 10 and VF, this trend was maintained in the C-carriers but not in TT. In the case of prose memory, of memory with interference, and of VF, schooling reduced the detrimental interaction between age and genotype. TheC825Tpolymorphism of GNB3 gene therefore influences memory and verbal fluency, being additive to the effects of age and partially mitigated by schooling.