Patented Biomarkers for the Early Detection of Ovarian Cancer

Ovarian cancer is responsible for the highest fatality rate among the gynecologic malignancies, and there is a great urgency in defining screening tests for its early detection. Presently, CA125 is the only serum marker recommended for early detection (in combination with transvaginal ultrasonography) in hereditary syndromes and for differential diagnosis in suspicious pelvic mass. However, given the complexity of the pathogenesis and of the tumor-host interaction, it is unlikely that a single serum biomarker bears sufficient information for the specific discrimination of ovarian cancer at its very early stage form other non-malignant pelvic lesions. Consistently, CA125 has demonstrated its utility for monitoring the therapy and prognosis, but owing to its scarce sensitivity and specificity it is not recommended for screening of ovarian cancer in asymptomatic patients. Recently, the introduction of high-throughput multiplex technologies, that allow to measure simultaneously a large number of molecules in the femtomolar range of concentration in the serum, has led to the definition of panels of biomarkers for the early detection of ovarian cancer. Here, we review the latest patents in this field

Resveratrol Reduces the Invasive Growth and Promotes the Acquisition of a Long-Lasting Differentiated Phenotype in Human Glioblastoma Cells

Malignant glioblastoma represents a challenge in the chemotherapy of brain tumors, because of its aggressive behavior characterized by chemoresistance, infiltrative diffusion, and high rate of recurrence and death. In this study, we used cultured human U87MG cells and primary human glioblastoma cultures to test the anticancer properties of resveratrol (RV), a phytoalexin abundantly present in a variety of dietary products. In U87MG cells, 100 \u3bcM RV elicited cell growth arrest by 48 h and bax-mediated cell toxicity by 96 h and greatly limited cell migration and invasion through matrigel. Both in U87MG cells and in primary glioblastoma cultures, the chronic administration of RV (100 \u3bcM for up to 96 h) decreased the expression of nestin (a brain (cancer) stem cells marker) but increased that of glial acidic fibrillary protein (a mature glial cell marker) and of \u3b2III-tubulin (a neuronal differentiation marker). Chronic treatment with RV increased the proportion of cells positive for senescence-associated \u3b2-galactosidase activity. This is the first report showing the ability of RV to induce glial-like and neuronal-like differentiation in glioblastoma cells. The beneficial effects of chronic RV supplementation lasted up to 96 h after its withdrawal from the culture medium. The present findings support the introduction of pulsed administration of this food-derived molecule in the chemotherapy regimen of astrocytomas

High Expression of Cathepsin D in Non-Hodgkin’s Lymphomas Negatively Impacts on Clinical Outcome

The lysosomal protease Cathepsin D (CD) has been implicated in the homeostasis of lymphatic tissues. We investigated whether the level of CD expression influences the progression and the clinical outcome in Non-Hodgkin’s Lymphomas (NHLs). The expression of CD was assessed by immunohistochemistry and immunofluorescence in biopsies of Diffuse Large B Cell Lymphomas (DLBCL, 35 cases), Follicular Lymphomas (FL, 9 cases of grade I-II plus 14 cases of grade IIIB), Chronic Lymphocytic Leukaemias (CLL, 17 cases) and Peripheral T-cell Lymphomas (PTCL, 5 cases). CD staining showed a cytoplasmic punctate pattern compatible with its lysosomal localization. Based on the level of CD expression and the proportion of positive cells, lymphomas were classified as ‘low expressing’ (< 20% of tumor cells) or ‘highly expressing’ (≥ 20% of tumor cells). Lymphomas highly expressing CD were associated with a worse stage (III-IV) at diagnosis (31/34 cases; p = 0.002) and with a poor clinical outcome (i.e., partial remission and death; 28/34 cases; p = 0.03). In the subgroup of aggressive/high grade of malignancy lymphomas (i.e., DLBCL, FL IIIB and PTCL), the Kaplan-Meier curve revealed a very low cumulative overall survival probability (~20% at 5 year) for patients bearing a NHL with > 40% CD-positive cells compared to that of patients bearing a NHL with < 20% CD-positive cells (~70% at 5 year). This correlation was statistically significant (log-rank test, p = 0.01). In Cox multivariate analysis CD failed to be a prognosticator independent of pathologic stage, though the hazard ratio confirmed the association of low expression with a better survival probability. These data indicate that the presence of a high percentage of CD-positive tumor cells negatively reflects on the progression of NHLs

Expression and Clinical Significance of the Autophagy Proteins BECLIN 1 and LC3 in Ovarian Cancer

Autophagy is dysregulated in cancer and might be involved in ovarian carcinogenesis. BECLIN-1, a protein that interacts with either BCL-2 or PI3k class III, plays a critical role in the regulation of both autophagy and cell death. Induction of autophagy is associated with the presence of vacuoles characteristically labelled with the protein LC3. We have studied the biological and clinical significance of BECLIN 1 and LC3 in ovary tumours of different histological types. The positive expression of BECLIN 1 was well correlated with the presence of LC3-positive autophagic vacuoles and was inversely correlated with the expression of BCL-2. The latter inhibits the autophagy function of BECLIN 1. We found that type I tumours, which are less aggressive than type II, were more frequently expressing high level of BECLIN 1. Of note, tumours of histologic grade III expressed low level of BECLIN 1. Consistently, high level of expression of BECLIN 1 and LC3 in tumours is well correlated with the overall survival of the patients. The present data are compatible with the hypotheses that a low level of autophagy favours cancer progression and that ovary cancer with upregulated autophagy has a less aggressive behaviour and is more responsive to chemotherapy

Collaborative Art: A Transformational Force within Communities

This article provides a new perspective on collaborative art as a transformational force to strengthen community and enhance well-being. We outline a best practices-based framework to foster community-based, collaborative art such as cocreated community murals. Specifically, we identify a strategic and successive process for collaborative art initiatives by integrating the academic literature on art, aesthetics, community, and consumer research together with the practices of arts organizations working to transform communities through participatory, cocreated art. The article highlights the contributions of this work to academic research, public policy, and community organizing efforts and outlines questions to encourage more researchers and practitioners to investigate the dynamics of collaborative art to transform communities

{OBINUTUZUMAB} {DOES} {NOT} {IMPROVE} {COMPLETE} {METHABOLIC} {RESPONSE} {BUT} {DOES} {NOT} {COMPROMISE} {MOBILIZATION} {OR} {ENGRAFTMENT} {OF} {AUTOLOGOUS} {PERIPHERAL} {BLOOD} {STEM} {CELLS} {IN} {DIFFUSE} {LARGE} B {CELL} {LYMPHOMA}: {RESULTS} {FROM} A {FIL} {PROSPECTIVE} {PHASE} {II} {STUDY} ({THE} {GIOTTO} {STUDY})

Salvage immunochemotherapy and transplant consolidation is the standard treatment for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We tested a combination of Obinutuzumab and DHAP for treating R/R DLBCL. The primary end point was the rate of complete metabolic response (CMR). Secondary end points were stem cell mobilization, stem cell engraftment, overall survival, and feasibility. In this prospective, phase-2, single-arm trial (EudraCT 2014-004014-17) patients received the standard three doses of Obinutuzumab for the first cycle, and then one dose. Patients with CMR were consolidated with an autologous stem cell transplantation (ASCT). An interim analysis was provided after the first 29 patients to confirm the initial null hypothesis that at least 10/29 patients would achieve CMR. Among the 29 patients evaluated for the first stage only six patients (6/29, 21%) achieved CMR, thus, study enrollment was stopped. Nine patients exhibited extra-hematologic toxicities &gt;= grade 3. Among the 19 patients that started stem cell mobilization, one failed (5%) and 18 achieved mobilization (95%). Of these 18 patients, nine were reinfused. Mobilization was observed in 16 patients (89%) after one or two apheresis rounds. The mean number of CD34 + cells mobilized was 5.8 x 10(6)/Kg (median: 5.5, IQR: 5-6.75). The mean number of reinfused CD34 + cells in the nine patients was 4.1 x 10(6)/Kg (median: 4.1, IQR: 3.5-5). Obinutuzumab combined with DHAP did not compromise stem cell mobilization or engraftment after ASCT in patients with DLBCL. However, Obinutuzumab + DHAP provided a lower CMR rate than expected