Genetic heterogeneity in breast cancer: the road to personalized medicine?

This is the final published version. It was originally published here: http://www.biomedcentral.com/1741-7015/11/151. DOI: 10.1186/1741-7015-11-151.More women die from breast cancer across the world today than from any other type of malignancy. The clinical course of breast cancer varies tremendously between patients. While some of this variability is explained by traditional clinico-pathological factors (including patient age, tumor stage, histological grade and estrogen receptor status), molecular profiling studies have defined breast cancer subtypes with distinct clinical outcomes. This mini-review considers recent studies which have used genomics technologies in an attempt to identify new biomarkers of prognosis and treatment response. These studies highlight the genetic heterogeneity that exists within breast cancers in space and time

COST PROJECTIONS FOR POST-CLOSURE CUSTODIAL CARE OF THE BARNWELL RADIOACTIVE WASTE DISPOSAL FACILITY

This document evaluates the adequacy of the Barnwell Extended Care Fund in light of the risks identified and concludes that it is sufficiently funded to cover the costs and uncertainties associated with activities planned for post-closure care of the facility. The report concludes that the fund is currently sufficiently funded to cover some but not all of the costs that might be incurred in responding to unplanned events and consequences. The document reviews background information pertinent to the post- closure monitoring and maintenance of the Barnwell low-level radioactive waste disposal facility (the Barnwell facility) and describes financial responsibility for post-closure activities

Combining Teletherapy and On-line Language Exercises in the Treatment of Chronic Aphasia: An Outcome Study

We report a 12-week outcome study in which nine persons with long-term chronic aphasia received individual and group speech-language teletherapy services, and also used on-line language exercises to practice from home between therapy sessions.  Participants were assessed at study initiation and completion using the Western Aphasia Battery, a portion of the Communicative Effectiveness Index, ASHA National Outcome Measurement System, and RIC Communication Confidence Rating Scale for Aphasia; additionally participants were polled regarding satisfaction at discharge.  Pre-treatment and post-treatment means were calculated and compared, and matched t-tests were used to determine significance of improvements following treatment, with patterns of independent on-line activity analyzed.  Analysis of scores shows that means improved on most measures following treatment, generally significantly: the WAB AQ improved +3.5 (p = .057); the CETI Overall (of items administered) — +17.8 (p = .01), and CCRSA Overall — + 10.4 (p = .0004).  Independent work increased with time, and user satisfaction following participation was high

Readiness to Change as a Mediator of the Effect of a Brief Motivational Intervention on Posttreatment Alcohol-Related Consequences of Injured Emergency Department Hazardous Drinkers

Evaluated impact of motivational enhancement (ME) of substance abuse treatment compared to relaxation training (RT) on sex without condoms (overall and involving substance use) 3 months following release among incarcerated adolescents. This randomized clinical trial involved 114 incarcerated adolescents from the Northeast. Regression analyses determined if treatment condition, baseline levels of depressive symptoms, and their interaction predicted condom non-use 3 months post-release, controlling for baseline condom non-use. Among those who reported fewer baseline depressive symptoms, those in ME condition reported significantly less condom non-use, in general and involving marijuana use compared with those in RT condition. Periods of incarceration represent opportunities to help juvenile detainees reduce behaviors that impact their health and the health of those with whom they interact in the community

Short-term change in growth of uterine leiomyoma: tumor growth spurts

To describe the short-term changes in growth of uterine leiomyomata (fibroids)

STING expression and response to treatment with STING ligands in premalignant and malignant disease.

Human papilloma virus positive (HPV+) tumors represent a large proportion of anal, vulvar, vaginal, cervical and head and neck squamous carcinomas (HNSCC) and late stage invasive disease is thought to originate from a premalignant state. Cyclic dinucleotides that activate STimulator of INterferon Genes (STING) have been shown to cause rapid regression of a range of advanced tumors. We aimed to investigate STING ligands as a novel treatment for papilloma. We tested therapies in a spontaneous mouse model of papilloma of the face and anogenital region that histologically resembles human HPV-associated papilloma. We demonstrate that STING ligands cause rapid regression of papilloma, associated with T cell infiltration, and are significantly more effective than Imiquimod, a current immunotherapy for papilloma. In humans, we show that STING is expressed in the basal layer of normal skin and lost during keratinocyte differentiation. We found STING was expressed in all HPV-associated cervical and anal dysplasia and was strongly expressed in the cancer cells of HPV+ HNSCC but not in HPV-unrelated HNSCC. We found no strong association between STING expression and progressive disease in non-HPV oral dysplasia and oral pre-malignancies that are not HPV-related. These data demonstrate that STING is expressed in basal cells of the skin and is retained in HPV+ pre-malignancies and advanced cancers, but not in HPV-unrelated HNSCC. However, using a murine HNSCC model that does not express STING, we demonstrate that STING ligands are an effective therapy regardless of expression of STING by the cancer cells

The exposure of the Great Barrier Reef to ocean acidification

The Great Barrier Reef (GBR) is founded on reef-building corals. Corals build their exoskeleton with aragonite, but ocean acidification is lowering the aragonite saturation state of seawater (Omega(a)). The downscaling of ocean acidification projections from global to GBR scales requires the set of regional drivers controlling Omega(a) to be resolved. Here we use a regional coupled circulation-biogeochemical model and observations to estimate the Omega(a) experienced by the 3,581 reefs of the GBR, and to apportion the contributions of the hydrological cycle, regional hydrodynamics and metabolism on Omega(a) variability. We find more detail, and a greater range (1.43), than previously compiled coarse maps of Omega(a) of the region (0.4), or in observations (1.0). Most of the variability in Omega(a) is due to processes upstream of the reef in question. As a result, future decline in Omega(a) is likely to be steeper on the GBR than currently projected by the IPCC assessment report

Clinical Development of Novel Drug-Radiotherapy Combinations.

Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumor, with sparing of adjacent normal tissues. There had been hope that the era of precision medicine would enhance the combination of radiotherapy with targeted anticancer drugs; however, this ambition remains to be realized. In view of this lack of progress, the FDA-AACR-ASTRO Clinical Development of Drug-Radiotherapy Combinations Workshop was held in February 2018 to bring together stakeholders and opinion leaders from academia, clinical radiation oncology, industry, patient advocacy groups, and the FDA to discuss challenges to introducing new drug-radiotherapy combinations to the clinic. This Perspectives in Regulatory Science and Policy article summarizes the themes and action points that were discussed. Intelligent trial design is required to increase the number of studies that efficiently meet their primary outcomes; endpoints to be considered include local control, organ preservation, and patient-reported outcomes. Novel approaches including immune-oncology or DNA-repair inhibitor agents combined with radiotherapy should be prioritized. In this article, we focus on how the regulatory challenges associated with defining a new drug-radiotherapy combination can be overcome to improve clinical outcomes for patients with cancer

Utilization of volumetric magnetic resonance imaging for baseline and surveillance imaging in Neuro-oncology.

The acquisition of volumetric post-contrast MRI has clear advantages in the interpretation of neuro-oncology studies but has yet to find its way into routine clinical practice beyond planning scans for surgery and radiotherapy. This commentary briefly highlights the benefits of these techniques whilst dispelling some of the perceived disadvantages