The Predictive Value of PITX2 DNA Methylation for High-Risk Breast Cancer Therapy: Current Guidelines, Medical Needs, and Challenges

High-risk breast cancer comprises distinct tumor entities such as triple-negative breast cancer (TNBC) which is characterized by lack of estrogen (ER) and progesterone (PR) and the HER2 receptor and breast malignancies which have spread to more than three lymph nodes. For such patients, current (inter)national guidelines recommend anthracycline-based chemotherapy as the standard of care, but not all patients do equally benefit from such a chemotherapy. To further improve therapy decision-making, predictive biomarkers are of high, so far unmet, medical need. In this respect, predictive biomarkers would permit patient selection for a particular kind of chemotherapy and, by this, guide physicians to optimize the treatment plan for each patient individually. Besides DNA mutations, DNA methylation as a patient selection marker has received increasing clinical attention. For instance, significant evidence has accumulated that methylation of the PITX2 (paired-like homeodomain transcription factor 2) gene might serve as a novel predictive and prognostic biomarker, for a variety of cancer diseases. This review highlights the current understanding of treatment modalities of high-risk breast cancer patients with a focus on recommended treatment options, with special attention on the future clinical application of PITX2 as a predictive biomarker to personalize breast cancer management

PCDD/F and dioxin-like PCB exposure in a coastal community via consumption of local seafood

A national study highlighted that, similar to other countries, seafood contributes a major proportion to polychlorinated-p-dibenzo dioxin (PCDD), dibenzofuran (PCDF) and dioxin-like polychlorinated biphenyl (PCB) exposure of Australians. As typical for national studies, the exposure assessment utilised contaminant concentrations in retail (sea)food. However, more than 80% of the Australian population lives within 50km of the coast, where recreational and/or subsistence fishing of local seafood is prominent. This study assessed TEQDP exposure for a coastal subpopulation who consume locally caught seafood from an area with low (background) TEQDP levels in sediments, which is typical for Australian nearshore marine systems. Despite low sediment levels, a previous study showed that TEQDP concentrations in local seafood were 25 fold higher than retail seafood. This study showed average monthly contaminant intake for the coastal community (ranged between 34 (best case) to 107 (worst case scenario) pg TEQ kg-1 bw month-1) was an order of magnitude higher than that estimated for the general population and was mainly driven by 2 to 6 fold higher seafood consumption rates. This highlights the need for information on seafood consumption patterns in coastal communities to better assess the contribution of locally sourced seafood to dietary PCDD/F and PCB exposure

Persistent organic pollutants in 9/11 world trade center rescue workers: reduction following detoxification

Abstract Exposure to toxins following the September 11, 2001 attack on and collapse of the World Trade Center (WTC) is of particular concern given the ultra fine particulate dust cloud, high temperature combustion, and months-long fire. Firefighters, paramedics, police and sanitation crews are among the approximately 40 000 personnel who labored for weeks and months on rescue and cleanup efforts. Many of the rescue workers have subsequently developed symptoms that remain unresolved with time. This study characterizes body burdens of polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and polychlorinated dioxins (PCDDs) in rescue workers and citizens exposed following the WTC collapse. Our research includes a pilot evaluation of a detoxification method aimed at reducing toxic burden. Many congeners were found at elevated levels, in ranges associated with occupational exposures. Post-detoxification testing revealed reductions in these congeners and despite the small study size, some reductions were statistically significant. Health symptoms completely resolved or were satisfactorily improved on completion of treatment. These results argue for a larger treatment study of this method and an overall treatment approach to address toxic burden

Assessment of polybrominated diphenyl ethers (PBDEs) in samples collected from indoor environments in South East Queensland, Australia

Polybrominated diphenyl ethers (PBDEs) are compounds that are used as flame retardants. Human exposure is suggested to be via food, dust and air. An assessment of PBDE exposure via indoor environments using samples of air, dust and surface wipes from eight sites in South East Queensland, Australia was conducted. For indoor air, ΣPBDEs ranged from 0.5 -179 pg/m3 for homes and 15 - 487 pg/m3 for offices. In dust, ΣPBDEs ranged from 87 - 733 ng/g dust and 583 - 3070 ng/g dust in homes and offices, respectively. PBDEs were detected on 9 out of 10 surfaces sampled and ranged from non-detectable to 5985 pg/cm2. Overall, the congener profiles for air and dust were dominated by BDE-209. This study demonstrated that PBDEs are ubiquitous in the indoor environments of selected buildings in South East Queensland and suggest the need for detailed assessment of PBDE concentrations using more sites to further investigate the factors influencing PBDE exposure in Australia

Evaluation of age, gender and regional concentration difference for dioxin-like chemicals in the Australia population

The results of this study provide a measure of the levels of dioxin-like compounds (polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls) in pooled blood serum collected throughout Australia in 2003. De-identified samples selected from surplus pathology samples were stratified on the basis of gender, region and age. In total 9090 samples were collected and analysed as 96 pools. Dioxin-like chemicals were detected in all strata. The mean and median levels expressed as TEQ values for all pooled samples were 10.9 +/- 1.0 pg TEQ g(-1) lipid and 8.3 pg TEQ g(-1) lipid. For males and females the mean levels were 10.4 +/- 0.6 pg TEQ g(-1) lipid and 11.5 +/- 1.5 pg TEQ g(-1) lipid, respectively. A direct relationship of increasing dioxin-like chemical levels with increasing age was observed and could be described by the following equation: Levels in blood expressed as pg TEQ g(-1) lipid = 3.3exp(0.025large) (r(2) = 0.87). No significant differences were observed in the levels of dioxin-like chemicals in samples collected from males and females. In addition, the levels of dioxin-like chemicals across the five regions were similar within each age range. In summary, the levels of dioxin-like chemicals in the Australian population are low compared to international levels and are similar across all regions of Australia within each designated age range. The levels of these chemicals increase with age and can be estimated if the age of an individual is known. (c) 2006 Elsevier Ltd. All rights reserved

Assessment of the Concentrations of Polybrominated Diphenyl Ether Flame Retardants in the Australian Population: Levels in Blood

Polybrominated diphenyl ethers (PBDEs), a common class of brominated flame retardants, are a ubiquitous part of our built environment, and for many years have contributed to improved public safety by reducing the flammability of everyday goods. Recently, PBDEs have come under increased international attention because of their potential to impact upon the environment and human health. Some PBDE compounds have been nominated for possible inclusion on the Stockholm Convention on Persistent Organic Pollutants, to which Australia is a Party. Work under the Stockholm Convention has demonstrated the capacity of some PBDEs to persist and accumulate in the environment and to be carried long distances. Much is unknown about the impact of PBDEs on living organisms, however recent studies show that some PBDEs can inhibit growth in colonies of plankton and algae and depress the reproduction of zooplankton. Laboratory mice and rats have also shown liver disturbances and damage to developing nervous systems as a result of exposure to PBDEs. In 2004, the Australian Government Department of the Environment and Water Resources began three studies to examine levels of PBDEs in aquatic sediments, indoor environments and human blood, as knowledge about PBDEs in Australia was very limited. The aim of these studies was to improve this knowledge base so that governments were in a better position to consider appropriate management actions. Due to the high costs for laboratory analysis of PBDEs, the number of samples collected for each study was limited and so caution is required when interpreting the findings. Nevertheless, these studies will provide governments with an indication of how prevalent PBDEs are in the Australian population and the environment and will also contribute to international knowledge about these chemicals. The Department of the Environment and Water Resources will be working closely with othergovernment agencies, industry and the community to investigate any further action that may be required to address PBDEs in Australia