Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies

Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor cells in these settings, cancer gene correction strategies may provide an opportunity for selective targeting without significant toxicity for normal nontumor cells. Both p53 and BRCA1 appear to inhibit cancer cells that lack mutations in these genes, suggesting that the so-called gene correction strategies may have broader potential than initially believed. Increasing knowledge of cancer genetics has identified these and other genes as potential targets for gene replacement therapy. Initial patient trials of p53 and BRCA1 gene therapy have provided some indications of potential efficacy, but have also identified areas of basic and clinical research that are needed before these approaches may be widely used in patient care

Species specific anaesthetics for fish anaesthesia and euthanasia.

There is a need to ensure that the care and welfare for fish maintained in the laboratory are to the highest standards. This extends to the use of anaesthetics for both scientific study, humane killing and euthanasia at end of life. An anaesthetic should not induce negative behaviours and fish should not seek to avoid the anaesthetic. Surprisingly little information is available to facilitate a humane choice of anaesthetic agent for fish despite over 100 years of use and the millions of fish currently held in thousands of laboratories worldwide. Using a chemotaxic choice chamber we found different species specific behavioural responses among four closely related fish species commonly held in the laboratory, exposed to three widely used anaesthetic agents. As previously found for zebrafish (Danio rerio), the use of MS-222 and benzocaine also appears to induce avoidance behaviours in medaka (Oryzias latipes); but etomidate could provide an alternative choice. Carp (Cyprinus carpio), although closely related to zebrafish showed avoidance behaviours to etomidate, but not benzocaine or MS-222; and rainbow trout (Oncorhynchus mykiss) showed no avoidance to the three agents tested. We were unable to ascertain avoidance responses in fathead minnows (Pimephales promelas) and suggest different test paradigms are required for that species

A Stakeholder-Informed Approach to the Identification of Criteria for the Prioritization of Zoonoses in Canada

Background: Zoonotic diseases account for over 60 % of all communicable diseases causing illness in humans and 75 % of recently emerging infectious diseases. As limited resources are available for the control and prevention of zoonotic diseases, it is necessary to prioritize diseases in order to direct resources into those with the greatest needs. The selection of criteria for prioritization has traditionally been on the basis of expert opinion; however, details of the methods used to identify criteria from expert opinion often are not published and a full range of criteria may not be captured by expert opinion. Methodology/Principal Findings: This study used six focus groups to identify criteria for the prioritization of zoonotic diseases in Canada. Focus groups included people from the public, animal health professionals and human health professionals. A total of 59 criteria were identified for prioritizing zoonotic diseases. Human-related criteria accounted for the highest proportion of criteria identified (55%), followed by animal-related criteria (26%) then pathogen/disease-related criteria (19%). Similarities and differences were observed in the identification and scoring of criteria for disease prioritization between groups; the public groups were strongly influenced by the individual-level of disease burden, the responsibility of the scientific community in disease prioritization and the experiences of recent events while the professional groups were influenced by the societal- and population-level of disease burden and political and public pressure

Breast imaging technology: Application of magnetic resonance imaging to angiogenesis in breast cancer

Magnetic resonance imaging (MRI) techniques enable vascular function to be mapped with high spatial resolution. Current methods for imaging in breast cancer are described, and a review of recent studies that compared dynamic contrast-enhanced MRI with histopathological indicators of tumour vascular status is provided. These studies show correlation between in vivo dynamic contrast measurements and in vitro histopathology. Dynamic contrast enhanced MRI is also being applied to assessment of the response of breast tumours to treatment

Nitric Oxide Synthase Inhibition Enhances the Antitumor Effect of Radiation in the Treatment of Squamous Carcinoma Xenografts

This study tests whether the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (L-NNA), combines favorably with ionizing radiation (IR) in controlling squamous carcinoma tumor growth. Animals bearing FaDu and A431 xenografts were treated with L-NNA in the drinking water. IR exposure was 10 Gy for tumor growth and survival studies and 4 Gy for ex vivo clonogenic assays. Cryosections were examined immunohistochemically for markers of apoptosis and hypoxia. Blood flow was assayed by fluorescent microscopy of tissue cryosections after i.v. injection of fluorospheres. Orally administered L-NNA for 24 hrs reduces tumor blood flow by 80% (p<0.01). Within 24 hrs L-NNA treatment stopped tumor growth for at least 10 days before tumor growth again ensued. The growth arrest was in part due to increased cell killing since a combination of L-NNA and a single 4 Gy IR caused 82% tumor cell killing measured by an ex vivo clonogenic assay compared to 49% by L-NNA or 29% by IR alone. A Kaplan-Meyer analysis of animal survival revealed a distinct survival advantage for the combined treatment. Combining L-NNA and IR was also found to be at least as effective as a single i.p. dose of cisplatin plus IR. In contrast to the in vivo studies, exposure of cells to L-NNA in vitro was without effect on clonogenicity with or without IR. Western and immunochemical analysis of expression of a number of proteins involved in NO signaling indicated that L-NNA treatment enhanced arginase-2 expression and that this may represent vasculature remodeling and escape from NOS inhibition. For tumors such as head and neck squamous carcinomas that show only modest responses to inhibitors of specific angiogenic pathways, targeting NO-dependent pro-survival and angiogenic mechanisms in both tumor and supporting stromal cells may present a potential new strategy for tumor control

A simple, reproducible method for monitoring the treatment of tumours using dynamic contrast-enhanced MR imaging

Dynamic contrast-enhanced MR imaging (DCE-MRI) may act as a biomarker for successful cancer therapy. Simple, reproducible techniques may widen this application. This paper demonstrates a single slice imaging technique. The image acquisition is performed in less than 500 ms making it relatively insensitive to respiratory motion. Data from phantom studies and a reproducibility study in solid human tumours are presented. The reproducibility study showed a coefficient of variation (CoV) of 19.1% for Ktrans and 15.8% for the initial area under the contrast enhancement curve (IAUC). This was improved to 16 and 13.9% if tumours of diameter less than 3 cm were excluded. The individual repeatability (the range within which individual measurements are expected to fall) was 30.6% for Ktrans and 26.5% for IAUC for tumours greater than 3 cm diameter. This approach to DCE–MRI image acquisition can be performed with standard clinical scanners, and data analysis is straightforward. For treatment trials with 10 patients in a cohort, the CoV implies that the method would be sensitive to a treatment effect of greater than 18%. The individual repeatability is well inside the 40% change shown to be important in clinical studies using this DCE–MRI technique

Age differences in mental health literacy

BACKGROUND: The community's knowledge and beliefs about mental health problems, their risk factors, treatments and sources of help may vary as a function of age. METHODS: Data were taken from an epidemiological survey conducted during 2003-2004 with a national clustered sample of Australian adults aged 18 years and over. Following the presentation of a vignette describing depression (n = 1001) or schizophrenia (n = 997), respondents were asked a series of questions relating to their knowledge and recognition of the disorder, beliefs about the helpfulness of treating professionals and medical, psychological and lifestyle treatments, and likely causes. RESULTS: Participant age was coded into five categories and cross-tabulated with mental health literacy variables. Comparisons between age groups revealed that although older adults (70+ years) were poorer than younger age groups at correctly recognising depression and schizophrenia, young adults (18-24 years) were more likely to misidentify schizophrenia as depression. Differences were also observed between younger and older age groups in terms of beliefs about the helpfulness of certain treating professionals and medical and lifestyle treatments for depression and schizophrenia, and older respondents were more likely to believe that schizophrenia could be caused by character weakness. CONCLUSION: Differences in mental health literacy across the adult lifespan suggest that more specific, age appropriate messages about mental health are required for younger and older age groups. The tendency for young adults to 'over-identify' depression signals the need for awareness campaigns to focus on differentiation between mental disorders

The real risks of steroid injection for plantar fasciitis, with a review of conservative therapies

This article presents a review of conservative therapies for plantar fasciitis pain reduction with a discussion of steroid therapy risks. The therapies reviewed include orthoses, stretching, extracorporeal shockwave, BTX-A, and corticosteroid injection/iontophoresis. These modes were included based on the availability of double blinded randomized controlled trials. We noted the following findings. Orthoses, regardless of type, can improve pain levels. Plantar stretching shows limited short-term benefit (1 month), but can reflect significant long-term improvement (10 months). Extracorporeal shockwave therapy shows equivocal benefit with some studies showing significant improvement and others showing none. Although BTX-A injections were the least studied, significant pain improvement was demonstrated in the short and long term. Steroid injection/iontophoresis showed significant improvement in the short term (1 month). Steroid therapy, when coupled with plantar stretching, can provide efficacious pain relief; however, steroid injections should be combined with ultrasound monitoring to reduce complications