Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

Assessment of the airborne sound insulation from mobility vibration measurements; a hybrid experimental numerical approach

International audienceA new measurement procedure is proposed to assess the airborne sound insulation of a partition under diffuse sound field excitation using mobility measurements combined with a numerical procedure. The advantage of this hybrid approach is that the diffuse acoustic field does not need to be physically created, thus avoiding problems related to the generation of such fields at low frequencies. Furthermore, the acoustic properties of both the source and receiving rooms will not affect the determination of the sound reduction index R. The proposed method is especially suited for frequencies below the so called Schroeder frequency of the room, and is complementary to the standardized measurement approaches as described in ISO 10140-2:2010. The measurement part of the proposed procedure involves the measurement of the mobility by forcing the partition along a grid of excitation points (e.g. by means of a shaker) and measuring its response along a grid of response points (e.g. by means of a scanning laser Doppler vibrometer). Using the resulting matrix of mobility transfer functions, the vibrational response of the partition excited by a diffuse acoustic field is numerically calculated , from which the radiated sound power is computed using the Rayleigh integral. Thus the reliance on source and receiving rooms used in standard sound insulation testing is removed entirely. The proposed method provides an estimate that only depends on the properties of the partition. The method was tested in an acoustic laboratory on a single layer glass plate of 1.35 × 1.54 m 2 , as well as on a funicular shell structure with dimensions of 3 × 3 m 2. Comparisons with analytical models and standardized ISO10140-2:2010 measurements confirm the validity of the results

Supplementary Material for: Clinical and Emergent Biomarkers and Their Relationship to the Prognosis of Ovarian Cancer

<b><i>Objective:</i></b> Ovarian cancer is the most lethal gynecological malignancy, but information relevant to prognosis and outcomes remain unknown. Here, we used statistical methods to focus specifically on interactions between candidate prognostic variables. <b><i>Methods and Results:</i></b> Univariate, multivariate, and elastic net modeling of 42 variables were applied to a cohort of 542 ovarian cancer patients with 393 episodes of cancer recurrence/death. In univariate analyses, overexpression of TFF3, MDM2, and p53 were associated with improved recurrence-free survival. In multivariate analyses adjusted for age, histology, stage, grade, ascites, and residual disease, overexpression of PR appeared to provide a protective effect [hazard ratio for >50% of cells positive, 0.64 (95% confidence interval 0.44-0.94) compared to <1%], and TFF3 showed a nonlinear association. Importantly, we observed no interactions among variables. However, patients with tumors with moderate TFF3 expression were at a marginally increased risk of recurrence, and patients with tumors with high expression were at a similar to slightly lower risk, compared to those with tumors with no TFF3 expression. <b><i>Conclusions:</i></b> Although no interactions among variables were observed, this study provides important precedent for seeking interactions between clinical and tumor variables in future studies