Biopsy confirmation of metastatic sites in breast cancer patients:clinical impact and future perspectives

Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome,and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations,the acquisition of tissue from metastatic deposits is not routine practice. As a consequence, therapeutic decisions for treatment in the metastatic setting are based on the features of the primary tumor. Reasons for this attitude include the invasiveness of the procedure and the unreliable outcome of biopsy, in particular for biopsies of lesions at complex visceral sites. Improvements in interventional radiology techniques mean that most metastatic sites are now accessible by minimally invasive methods, including surgery. In our opinion, since biopsies are diagnostic and changes in biological features between the primary and secondary tumors can occur, the routine biopsy of metastatic disease needs to be performed. In this review, we discuss the rationale for biopsy of suspected breast cancer metastases, review issues and caveats surrounding discordance of biomarker status between primary and metastatic tumors, and provide insights for deciding when to perform biopsy of suspected metastases and which one (s) to biopsy. We also speculate on the future translational implications for biopsy of suspected metastatic lesions in the context of clinical trials and the establishment of bio-banks of biopsy material taken from metastatic sites. We believe that such bio-banks will be important for exploring mechanisms of metastasis. In the future,advances in targeted therapy will depend on the availability of metastatic tissue

TDP-43 Identified from a Genome Wide RNAi Screen for SOD1 Regulators

Amyotrophic Lateral Sclerosis (ALS) is a late-onset, progressive neurodegenerative disease affecting motor neurons in the brain stem and spinal cord leading to loss of voluntary muscular function and ultimately, death due to respiratory failure. A subset of ALS cases are familial and associated with mutations in superoxide dismutase 1 (SOD1) that destabilize the protein and predispose it to aggregation. In spite of the fact that sporadic and familial forms of ALS share many common patho-physiological features, the mechanistic relationship between SOD1-associated and sporadic forms of the disease if any, is not well understood. To better understand any molecular connections, a cell-based protein folding assay was employed to screen a whole genome RNAi library for genes that regulate levels of soluble SOD1. Statistically significant hits that modulate SOD1 levels, when analyzed by pathway analysis revealed a highly ranked network containing TAR DNA binging protein (TDP-43), a major component of aggregates characteristic of sporadic ALS. Biochemical experiments confirmed the action of TDP-43 on SOD1. These results highlight an unexpected relationship between TDP-43 and SOD1 which may have implications in disease pathogenesis

Temporal variability in shell mound formation at Albatross Bay, northern Australia

We report the results of 212 radiocarbon determinations from the archaeological excavation of 70 shell mound deposits in the Wathayn region of Albatross Bay, Australia. This is an intensive study of a closely co-located group of mounds within a geographically restricted area in a wider region where many more shell mounds have been reported. Valves from the bivalve Tegillarcca granosa were dated. The dates obtained are used to calculate rates of accumulation for the shell mound deposits. These demonstrate highly variable rates of accumulation both within and between mounds. We assess these results in relation to likely mechanisms of shell deposition and show that rates of deposition are affected by time-dependent processes both during the accumulation of shell deposits and during their subsequent deformation. This complicates the interpretation of the rates at which shell mound deposits appear to have accumulated. At Wathayn, there is little temporal or spatial consistency in the rates at which mounds accumulated. Comparisons between the Wathayn results and those obtained from shell deposits elsewhere, both in the wider Albatross Bay region and worldwide, suggest the need for caution when deriving behavioural inferences from shell mound deposition rates, and the need for more comprehensive sampling of individual mounds and groups of mounds

Exploring Doctor–Patient Communication in Immigrant Australians with Type 2 Diabetes: A Qualitative Study

OBJECTIVE: The study explored the perceptions of Australian immigrants about their interactions with doctors regarding the diagnosis, treatment, and management of type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: In-depth interviews were conducted with 30 men and women from Greek, Indian, Chinese, and Pacific Island backgrounds living in Melbourne, Australia, to elicit their perceptions of the management of diabetes and its impact. Participants were recruited through a convenience sample of general practitioners and community organizations providing support to people living with diabetes. Topics discussed included initial reaction to diagnosis, patient—health care provider communication, and the influence of message framing on the perception of the quality of the doctor–patient relationship. Transcripts were coded and analyzed by both authors. RESULTS: Numerous issues facilitate or inhibit constructive and positive relationships between doctors and patients with type 2 diabetes. Patients reported difficulty in absorbing all the information provided to them at early consultations, and experienced difficulty comprehending the practical aspects of management. Styles of communication and discourses of normalization and catastrophe influenced participants’ responses. CONCLUSION: Doctors face a complex task in encouraging behavioral change and adherence and establishing and maintaining a supportive relationship with patients. The timing and technical complexity of communication about diabetes, its management, and the prevention of complications require further attention

The Osteology of the Basal Archosauromorph Tasmaniosaurus triassicus from the Lower Triassic of Tasmania, Australia

Proterosuchidae are the most taxonomically diverse archosauromorph reptiles sampled in the immediate aftermath of the Permo-Triassic mass extinction and represent the earliest radiation of Archosauriformes (archosaurs and closely related species). Proterosuchids are potentially represented by approximately 15 nominal species collected from South Africa, China, Russia, Australia and India, but the taxonomic content of the group is currently in a state of flux because of the poor anatomic and systematic information available for several of its putative members. Here, the putative proterosuchid Tasmaniosaurus triassicus from the Lower Triassic of Hobart, Tasmania (Australia),is redescribed. The holotype and currently only known specimen includes cranial and postcranial remains and the revision of this material sheds new light on the anatomy of the animal, including new data on the cranial endocast. Several bones are re-identified or reinterpreted, contrasting with the descriptions of previous authors. The new information provided here shows that Tasmaniosaurus closely resembles the South African proterosuchid Proterosuchus, but it differed in the presence of, for example, a slightly downturned premaxilla, a shorter anterior process of maxilla, and a diamond-shaped anterior end of interclavicle. Previous claims for the presence of gut contents in the holotype of Tasmaniosaurus are considered ambiguous. The description of the cranial endocast of Tasmaniosaurus provides for the first time information about the anatomy of this region in proterosuchids. The cranial endocast preserves possibly part of the vomero-nasal (= Jacobson's) system laterally to the olfactory bulbs. Previous claims of the absence of the vomero-nasal organs in archosaurs, which is suggested by the extant phylogenetic bracket, are questioned because its absence in both clades of extant archosaurs seems to be directly related with the independent acquisition of a non-ground living mode of life

Gene signatures of breast cancer progression and metastasis

Breast cancer is a heterogeneous disease. Patient outcome varies significantly, depending on prognostic features of patients and their tumors, including patient age, menopausal status, tumor size and histology, nodal status, and so on. Response to treatment also depends on a series of predictive factors, such as hormone receptor and HER2 status. Current treatment guidelines use these features to determine treatment. However, these guidelines are imperfect, and do not always predict response to treatment or survival. Evolving technologies are permitting increasingly large amounts of molecular data to be obtained from tumors, which may enable more personalized treatment decisions to be made. The challenge is to learn what information leads to improved prognostic accuracy and treatment outcome for individual patients